Protein Science

Cover image for Vol. 26 Issue 8

Edited By: Brian W. Matthews

Impact Factor: 2.523

ISI Journal Citation Reports © Ranking: 2016: 158/286 (Biochemistry & Molecular Biology)

Online ISSN: 1469-896X

Virtual Issues

Virtual Issue 10, 2017: Protein Science in Canada

Virtual Issue 9, 2016: Highlighting 25 Years of Protein Science

Virtual Issue 8, July 2014: Celebrating the 28th Annual Protein Society Symposium

Virtual Issue 7: Proteins in Motion

Virtual Issue 6, February 12: Protein Annotation

Virtual Issue 5, July 2011: Research Frontiers

Virtual Issue 4, May 2011: Pacific Rim

Virtual Issue 3, July 2010: Protein Folding

Virtual Issue 2, November 2009: Learning about Proteins

Virtual Issue 1, May 2009: Structure of Myoglobin

Virtual Issue 10, 2017: Protein Science in Canada

Edited by Anar Murphy and Brian W. Matthews*

*Corresponding address: Institute of Molecular Biology, University of Oregon, Eugene, OR 97403 USA E-mail:

This year’s 31st Annual Symposium of the Protein Society will take place in the City of Saints – Montreal, Canada from July 24 to 27. To commemorate this spectacular event and to celebrate our Canadian authors, we present this Virtual Issue with the best recent Canadian papers published in Protein Science. And we wish Canada its Happy 150th Birthday!

The thirteen papers presented in this Virtual Issue are only a few of many great articles that we have received and published from Canada since Protein Science was founded by Dr. Hans Neurath in 1992. In this 1993 study from Cygler and coworkers [1], the authors presented a comprehensive structural analysis of hydrolytic enzymes esterases, lipases, and related proteins based on the X-ray structures of Torpedo californica acetylcholinesterase and Georichum candidum lipase. They obtained an improved alignment of a collection of 32 related amino acid residues in these enzymes and found 24 residues to be invariant in 29 sequences, and an additional 49 to be well conserved.

Protein research heavily relies on state-of-the-art protein purification, imaging and characterization techniques. In this Review article, Brown and Ladizhansky [2] discuss membrane protein sample requirements, recent advances in Solid-state Nuclear Magnetic Resonance (SSNMR) technologies with a primary focus on the magic angle spinning SSNMR, and their applications to characterize membrane proteins in situ, either in cell membranes or whole cells. Using complementary potentiometric and NMR spectroscopic methods, Garcia-Moreno, McIntosh and coworkers [3] report the revised intrinsic pKa value of the arginine guanidinium group of 13.8±1, which is substantially higher than the traditionally reported value of ~12. This finding might explain why arginines remain predominantly charged in non-polar environments, unlike cysteine, aspartic acid, histidine, lysine, glutamic acid, and tyrosine.

Forman-Kay and coworkers [4] report significant differences between α- and γ-synuclein secondary structure propensities by an artful combination of NMR spectroscopy, a simple new technique for re-referencing chemical shifts and a new method that combines different chemical shifts into a single residue-specific secondary structure propensity (SSP) score. This approach is highly effective for both disordered and folded proteins, and therefore can be used to investigate human diseases associated with intrinsically disordered proteins. Meiering and coworkers [5] take a different approach to provide key information for understanding the mechanisms and energetics underlying normal maturation of SOD1, Cu, Zn-superoxide dismutase (SOD1) implicated in causing amyotrophic lateral sclerosis, as well as toxic SOD1 misfolding pathways associated with disease. They use isothermal titration calorimetry and size exclusion chromatography to build a quantitative data set for accurate prediction of protein-protein association.

Mass spectrometry (MS) is another common method used in protein science. In Special Issue on Mass Spectrometry in Structural Biology, Schriemer and coworkers [6] presented hydrogen exchange (HX)-MS2 that produces two-fold higher α/β-tubulin sequence depth at a peptide utilization rate of 74% in the data from conformational analysis of microtubules treated with dimeric kinesin MCAK, compared to a conventional Mascot-driven HX-MS approach (a utilization rate of 44%). Burke and coworkers [7] report a hybrid hydrogen-deuterium exchange – MS/crystallographic strategy to: (i) identify dynamic regions within type III phosphatidylinositol 4 kinase beta (PI4KIIIβ) in complex with the GTPase Rab11, and (II) determine structures of PI4KIIIβ in an Apo state and bound to the inhibitor BQR695 in complex with both GTPγS and GDP loaded Rab11.

Cryo-Electron Microscopy is a powerful tool to study protein structure, which was highlighted in the namesake Special Issue this January. One of the studies published in this Special Issue from Kollman and coworkers [8] report the structure of the MamK filament at ~6.5Å. The MamK protein filaments are responsible for anchoring of magnetosomes and therefore their alignment in the magnetotactic bacteria.

In 2015, Roberto Chico guest edited Protein Science Special Issue “Protein Engineering in the 21st Century” dedicated to the inaugural Protein Engineering Canada Conference held on June 20-22, 2014, in Ottawa, Canada. Three papers from this Special Issue are included in this Virtual Issue. Using a dataset of 108 proteins including two-state and multistate folders, Meiering and coworkers [9] find that protein unfolding rates correlated as strongly as folding rates with native structure. They suggest that choosing a scaffold for protein engineering may require a compromise between a simple topology that will fold and unfold sufficiently quickly, and a complex kinetically stable topology that will fold and unfold slowly. In this proof-of-concept article, Frappier and Najmanovich [10] test recently introduced ENCoM, an elastic network atomic contact model, on a curated extensive non-redundant dataset of mesophile/thermophile homolog pairs. They can be discerned from each other based on a measure of vibrational entropy on normal mode analysis with 60% of thermophile proteins being rigid at the same high temperatures as their mesophile counterpart. This finding and mutational analysis carry important implications to protein engineering. Doucet and coworkers [11] interrogate clavulanate resistance in BlaC β-lactamase from Mycobacterium tuberculosis by performing combinatorial active-site replacements in BlaC. They find that the prolonged stability and activity of generated mycobacterial variants, specifically in double mutants R220S-K234R and S130G-K234R, after 24 h incubation with a clinically relevant does of clavulanate (g/ml, 25 M) correlate well with mycobacterial proliferation. A review by Strynadka and coworkers [12] gives a comprehensive overview of b-lactam antibiotics from a structural perspective in light of the recent multidrug antibiotic resistance crisis.

In the following year Protein Science published Special Issue on Protein Evolution and Design. An important contribution by Miton and Tohuruki [13] report a systematic survey of mutational epistasis, non-additive mutational effects, occurring within nine adaptive enzyme trajectories. This work uncovers the prevalence of positive epistasis in enzyme adaptive evolution during a later stage of trajectory, and therefore the authors suggest it as an important tool in protein design and engineering for practical uses.

Canada has an especially distinguished history in protein science, including the 1921 discovery of insulin by Banting and Best. That tradition of excellence has continued to this day, and in this context it is noteworthy that the article by Miton and Tohuruku [13] was chosen as one of the two best papers published last year in Protein Science.

Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins
Miroslaw Cygler, Joseph D. Schrag, Joel L. Sussman, Michal Harel, Israel Silman, Mary K. Gentry and Bhupendra P. Doctor

Membrane proteins in their native habitat as seen by solid-state NMR spectroscopy.
Leonid S. Brown and Vladimir Ladizhansky

Arginine: Its pKa value revisited
Carolyn A. Fitch, Gerald Platzer, Mark Okon, Bertrand Garcia-Moreno E. and Lawrence P. McIntosh

Sensitivity of secondary structure propensities to sequence differences between α- and γ-synuclein: Implications for fibrillation
Joseph A. Marsh, Vinay K. Singh, Zongchao Jia and Julie D. Forman-Kay

Destabilization of the dimer interface is a common consequence of diverse ALS-associated mutations in metal free SOD1.
Helen R. Broom, Jessica A. O. Rumfeldt, Kenrick A. Vassall and Elizabeth M. Meiering

HX-MS2 for high performance conformational analysis of complex protein states.
Kyle M. Burns, Vladimir Sarpe, Mike Wagenbach, Linda Wordeman and David C. Schriemer

Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11.
Melissa L. Fowler, Jacob A. McPhail, Meredith L. Jenkins, Glenn R. Masson, Florentine U. Rutaganira, Kevan M. Shokat, Roger L. Williams and John E. Burke

Structure of the magnetosome-associated actin-like MamK filament at subnanometer resolution.
Julien R.C. Bergeron, Rachel Hutto, Ertan Ozyamak, Nancy Hom, Jesse Hansen, Olga Draper, Meghan E. Byrne, Sepehr Keyhani, Arash Komeili and Justin M. Kollman

Protein unfolding rates correlate as strongly as folding rates with native structure.
Aron Broom, Shachi Gosavi and Elizabeth M. Meiering

Vibrational entropy differences between mesophile and thermophile proteins and their use in protein engineering.
Vincent Frappier and Rafael Najmanovich

Combinatorial active-site variants confer sustained clavulanate resistance in BlaC β-lactamase from Mycobacterium tuberculosis.
Philippe Egesborg, Hélène Carlettini, Jordan P. Volpato and Nicolas Doucet

One ring to rule them all: Current trends in combating bacterial resistance to the β-lactams.
Dustin T. King, Solmaz Sobhanifar and Natalie C. J. Strynadka

How mutational epistasis impairs predictability in protein evolution and design.
Charlotte M. Miton and Nobuhiko Tokuriki



Virtual Issue 9, 2016: Highlighting 25 Years of Protein Science

Edited by Brian W. Matthews*

*Corresponding address: Institute of Molecular Biology, University of Oregon, Eugene, OR 97403 USA E-mail:

January 2017 will mark the 25th anniversary of the publication of Protein Science. Established in the early days of the Protein Society, and thanks in large part to the enthusiasm of Ralph Bradshaw in the face of considerable skepticism, the journal is now central to the mission of the Society.

In an excellent overview, Mark Hermodson has described the birth of the Protein Society, and the subsequent launching of Protein Science. Mark was the Society President at the time that the journal was introduced and, in his recollection, one can relive his concern that the cost of publication would bankrupt the Society. Thanks to a generous loan from the ASBMB, such a catastrophe was avoided. Mark can now have the satisfaction of knowing that the journal has not only become a highly-regarded scientific forum for protein scientists worldwide, but also helps support the Society’s symposia and other activities.

The purpose of this Virtual Issue is to highlight some of the best-received articles which have been published during the history of the journal.

The most-referenced article “of all time”, with over 2500 citations, is the 1995 report from Nick Pace’s group “How to measure and predict the molar absorption-coefficient of a protein”.2 It includes a simple way to predict the absorption coefficient of a protein from knowledge of the content of tryptophan, tyrosine and cystine. The use of this formula no doubt explains the popularity of the article. It’s an instructive lesson in how to write a successful paper – i.e. it isn’t necessary to be super-sophisticated – just introduce a new result, a new method or a new insight which is useful to your peers. There are many other examples where authors have introduced a new method or new approach which has been widely adopted. One example is Hutchinson and Thornton’s introduction of a program to identify and analyze structural motifs in proteins. Another is the procedure of Colovos and Yeates to differentiate between correctly and incorrectly determined regions of protein structures based on characteristic atom-atom interactions. Yet another case is a method from Andrej Sali and coworkers to model loops in protein structures.

1995 was something of a banner year for the Pace lab because in the same year that they published Reference 2, they also contributed another very highly-cited report, this showing that denaturant m values, the dependence of the free energy of unfolding on denaturant concentration, correlate strongly with the amount of protein surface exposed to solvent upon unfolding.

Yet another well-received article in 1995 was the review of Ken Dill and coworkers showing that computer simulations of simple, exact lattice models can provide important insights into the principles of protein structure, stability and folding.

There are many other early “Protein Science Classics” which the reader would immediately recognize. Just one example is provided by the article of Bennett, Schlunegger and Eisenberg: “3D domain swapping: A mechanism for oligomer assembly”.

To bridge from the “classic” period to more recent years, we highlight two related articles from Vladimir Uversky. The first, published in 2002, waits for an answer: “Natively unfolded proteins: A point where biology waits for physics”. The second, in 2013, repeats the question: “A decade and a half of protein intrinsic disorder: Biology still waits for physics”. These two reports highlight the ever-increasing appreciation of the roles played by disordered or partially-disordered proteins. In one example, the well-cited 2012 article by Keith Dunker and colleagues argues that intrinsic disorder may allow the same region of a protein to bind different partners.

The most highly-cited report in 2013, from Shing Ho and colleagues, discusses halogen bonding (or X-bonding). These electrostatically driven, directional interactions, which often involve halogenated compounds, can contribute to the specificity of molecular interactions in both proteins and nucleic acids.

Within recent years, the impact of mass spectrometry has become more pervasive, exemplified by multiple citations of the report of Igor Kaltashov and colleagues. In this context, the August 2015 issue of Protein Science was a special issue on mass spectrometry, edited by Albert Heck. A number of the articles in that issue [Marcoux et. A., 2015; Nguyen-Hyuhn et al., 2015; Erba and Petoso, 2015; Konijnenberg et al., 2015] are already receiving significant attention. One might single out, in particular, the report by Julien Marcoux and colleagues, on the use of ion mobility and native mass spectrometry to characterize a lysine-linked antibody drug conjugate.

Not surprisingly, there has always been, and continues to be an ongoing interest in problems of medical relevance. The recent description of the structure of a human insulin-regulated aminopeptidase with specificity for cyclic peptides, from , is one example. Likewise, there has been much interest in the recent article from Michael Kay’s group on the design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets.

Readers of Protein Science can also look forward to strong contributions in the future. In particular, July 2016 will be a special issue on Protein Evolution and Design, edited by Dan Bolon, Dan Tawfik and David Baker. As Editor, I have been honored to be associated with the journal, and thank all those who have contributed for their ongoing support.

The Protein Society: Celebrating 20 years in 2006—The founding and early years
Mark Hermodson

How to measure and predict the molar absorption coefficient of a protein.
C. Nick Pace, Felix Vajdos, Lanette Fee, Gerald Grimsley and Theronica Gray

PROMOTIF—A program to identify and analyze structural motifs in proteins
E. Gail Hutchinson and Janet M. Thornton

Verification of protein structures: Patterns of nonbonded atomic interactions
Chris Colovos and Todd O. Yeates

Modeling of loops in protein structures.
András Fiser, Richard Kinh Gian Do and Andrej Šali

Denaturant m values and heat capacity changes: Relation to changes in accessible surface areas of protein unfolding.
Jeffrey K. Myers, C. Nick Pace and J. Martin Scholtz

Principles of protein folding — A perspective from simple exact models.
Ken A. Dill, Sarina Bromberg, Kaizhi Yue, Hue Sun Chan, Klaus M. Ftebig, David P. Yee and Paul D. Thomas

3D domain swapping: A mechanism for oligomer assembly.
Melanie J. Bennett, Michael P. Schlunegger and David Eisenberg

Natively unfolded proteins: A point where biology waits for physics.
Vladimir N. Uversky

A decade and a half of protein intrinsic disorder: Biology still waits for physics.
Vladimir N. Uversky

Exploring the binding diversity of intrinsically disordered proteins involved in one-to-many binding.
Wei-Lun Hsu, Christopher J. Oldfield, Bin Xue, Jingwei Meng, Fei Huang, Pedro Romero, Vladimir N. Uversky and A. Keith Dunker

Halogen bonding (X-bonding): A biological perspective.
Matthew R. Scholfield, Crystal M. Vander Zanden, Megan Carter and P. Shing Ho

Mass spectrometry-based methods to study protein architecture and dynamics.
Igor A. Kaltashov, Cedric E. Bobst and Rinat R. Abzalimov

Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.
Julien Marcoux, Thierry Champion, Olivier Colas, Elsa Wagner-Rousset, Nathalie Corvaïa, Alain Van Dorsselaer, Alain Beck and Sarah Cianférani

Chemical cross-linking and mass spectrometry to determine the subunit interaction network in a recombinant human SAGA HAT subcomplex.
Nha-Thi Nguyen-Huynh, Grigory Sharov, Clément Potel, Pélagie Fichter, Simon Trowitzsch, Imre Berger, Valérie Lamour, Patrick Schultz, Noëlle Potier and Emmanuelle Leize-Wagner

The emerging role of native mass spectrometry in characterizing the structure and dynamics of macromolecular complexes.
Elisabetta Boeri Erba and Carlo Petosi

Top-down mass spectrometry of intact membrane protein complexes reveals oligomeric state and sequence information in a single experiment.
Albert Konijnenberg, Ludovic Bannwarth, Duygu Yilmaz, Armağan Koçer, Catherine Venien-Bryan and Frank Sobott

Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides.
Stefan J. Hermans, David B. Ascher, Nancy C. Hancock, Jessica K. Holien, Belinda J. Michell, Siew Yeen Chai, Craig J. Morton and Michael W. Parker

Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets.
Tracy R. Clinton, Matthew T. Weinstock, Michael T. Jacobsen, Nicolas Szabo-Fresnais, Maya J. Pandya, Frank G. Whitby, Andrew S. Herbert, Laura I. Prugar, Rena McKinnon, Christopher P. Hill, Brett D. Welch, John M. Dye, Debra M. Eckert and Michael S. Kay



Virtual Issue 8, July 2014: Celebrating the 28th Annual Protein Society Symposium

Celebrating the 28th Annual Protein Society Symposium

This virtual issue of Protein Science, the official journal of the Protein Society, brings together a collection of recent papers representing core areas of research featured at the 2014 symposium and of particular interest to society members: Protein Stability, Protein Evolution, Membranes and Proteins, and Proteins in Disease and Therapeutics.

Introduction to the Virtual Issue
Amy E. Keating


Contribution of hydrogen bonds to protein stability
C. Nick Pace, Hailong Fu, Katrina Lee Fryar, John Landua, Saul R. Trevino, David Schell, Richard L. Thurlkill, Satoshi Imura, J. Martin Scholtz, Ketan Gajiwala, Jozef Sevcik, Lubica Urbanikova, Jeffery K. Myers, Kazufumi Takano, Eric J. Hebert, Bret A. Shirley and Gerald R. Grimsley

Quantitative theory of hydrophobic effect as a driving force of protein structure
Nikolay Perunov and Jeremy L. England

Biophysical characterization of mutants of Bacillus subtilis lipase evolved for thermostability: Factors contributing to increased activity retention
Wojciech Augustyniak, Agnieszka A. Brzezinska, Tjaard Pijning, Hans Wienk, Rolf Boelens, Bauke W. Dijkstra and Manfred T. Reetz

Insulin analog with additional disulfide bond has increased stability and preserved activity
Tine N. Vinther, Mathias Norrman, Ulla Ribel, Kasper Huus, Morten Schlein, Dorte B. Steensgaard, Thomas Å. Pedersen, Ingrid Pettersson, Svend Ludvigsen, Thomas Kjeldsen, Knud J. Jensen and František Hubálekz

A method to rationally increase protein stability based on the charge-charge interaction, with application to lipase LipK107
Lujia Zhang, Xiaomang Tang, Dongbing Cui, Zhiqiang Yao, Bei Gao, Shuiqin Jiang, Bo Yin, Y. Adam Yuan and Dongzhi Wei

Ribonuclease A suggests how proteins self-chaperone against amyloid fiber formation.
Poh K. Teng, Natalie J. Anderson, Lukasz Goldschmidt, Michael R. Sawaya, Shilpa Sambashivan and David Eisenberg


The interface of protein structure, protein biophysics, and molecular evolution
David A. Liberles, Sarah A. Teichmann, Ivet Bahar, Ugo Bastolla, Jesse Bloom, Erich Bornberg-Bauer, Lucy J. Colwell, A. P. Jason de Koning, Nikolay V. Dokholyan, Julian Echave, Arne Elofsson, Dietlind L. Gerloff, Richard A. Goldstein, Johan A. Grahnen, Mark T. Holder, Clemens Lakner, Nicholas Lartillot, Simon C. Lovell, Gavin Naylor, Tina Perica, David D. Pollock, Tal Pupko, Lynne Regan, Andrew Roger, Nimrod Rubinstein, Eugene Shakhnovich, Kimmen Sjölander, Shamil Sunyaev, Ashley I. Teufel, Jeffrey L. Thorne, Joseph W. Thornton, Daniel M. Weinreich and Simon Whelan

Insights into the evolution of lanthipeptide biosynthesis
Yi Yu, Qi Zhang and Wilfred A. van der Donk

Sequence variation and structural conservation allows development of novel function and immune evasion in parasite surface protein families
Matthew K. Higgins and Mark Carrington

Evolution of crystallins for a role in the vertebrate eye lens
Christine Slingsby, Graeme J. Wistow and Alice R. Clark

Correlating structure and function during the evolution of fibrinogen-related domains
Russell F. Doolittle, Kyle McNamara and Kevin Lin

Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites
Austin Elam, Travis P. Schrank, Andrew J. Campagnolo and Vincent J. Hilser


A common landscape for membrane-active peptides
Nicholas B. Last, Diana E. Schlamadinger and Andrew D. Miranker

Structural evolution and membrane interactions of Alzheimer's amyloid-beta peptide oligomers: New knowledge from single-molecule fluorescence studies
Robin D. Johnson, Duncan G. Steel and Ari Gafni

Cholesterol as a co-solvent and a ligand for membrane proteins
Yuanli Song, Anne K. Kenworthy and Charles R. Sanders

A knowledge-based potential highlights unique features of membrane α-helical and β-barrel protein insertion and folding
Daniel Hsieh, Alexander Davis and Vikas Nanda

Structural basis for proton conduction and inhibition by the influenza M2 protein
Mei Hong and William F. DeGrado

Conformational analysis of the full-length M2 protein of the influenza A virus using solid-state NMR
Shu Yu Liao, Keith J. Fritzsching and Mei Hong

Modeling the membrane environment has implications for membrane protein structure and function: Influenza A M2 protein
Huan-Xiang Zhou and Timothy A. Cross

Open and shut: Crystal structures of the dodecylmaltoside solubilized mechanosensitive channel of small conductance from Escherichia coli and Helicobacter pylori at 4.4 Å and 4.1 Å resolutions
Jeffrey Y. Lai, Yan Shuen Poon, Jens T. Kaiser and Douglas C. Rees

Measuring membrane protein bond orientations in nanodiscs via residual dipolar couplings
Stefan Bibow, Marta G. Carneiro, T. Michael Sabo, Claudia Schwiegk, Stefan Becker, Roland Riek and Donghan Lee


Resistance to antibiotics targeted to the bacterial cell wall
I. Nikolaidis, S. Favini-Stabile and A. Dessen

Morin hydrate inhibits amyloid formation by islet amyloid polypeptide and disaggregates amyloid fibers
Harris Noor, Ping Cao and Daniel P. Raleigh

Characterizing antiprion compounds based on their binding properties to prion proteins: Implications as medical chaperoness
Yuji O. Kamatari, Yosuke Hayano, Kei-ichi Yamaguchi, Junji Hosokawa-Muto and Kazuo Kuwata

The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors
Sebastian M. Lambert, David R. Langley, James A. Garnett, Richard Angell, Katy Hedgethorne, Nicholas A. Meanwell and Steve J. Matthews


Virtual Issue 7: Proteins in Motion

Proteins are not static entities but instead must breathe, vibrate and undergo large domain movements in order to perform their functions. In addition, proteins sample many different interconverting structures in conformational ensembles, both during their folding and once they reach stable native folded states. Three-dimensional atomic resolution structures of proteins offer incredible insight, and we rely heavily on the information they provide. But a great deal of research through the past few decades has been directed at understanding the motions of proteins at many different time scales, from the rapid rotations of methyl groups to the relatively lethargic movements of domains with respect to each other. Regulation of protein activity, allostery, binding and catalysis all depend on the nature of protein motions. This Virtual Issue gathers papers that describe exciting current research on protein dynamics. The majority of contributions highlighted here have appeared in Protein Science in the last three years. In addition, seminal highly cited papers on proteins in motion from earlier issues of Protein Science are also included.

Introduction to the Virtual Issue
Gierasch, Lila M


Determination of amide hydrogen-exchange by mass-spectrometry - a new tool for protein-structure elucidation
Zhang ZQ, Smith DL

Determinants of protein hydrogen exchange studied in equine cytochrome c
Milne JS, Mayne L, Roder H, Wand AJ, Englander SW

Locally accessible conformations of proteins: Multiple molecular dynamics simulations of crambin
Caves LSD, Evanseck JD, Karplus M

Weak alignment offers new NMR opportunities to study protein structure and dynamics
Bax A

Protein dynamics viewed by hydrogen exchange
Skinner JJ, Lim WK, Bedard S, Black BE, Englander SW

Probing local structural fluctuations in myoglobin by size-dependent thiol-disulfide exchange
Stratton MM, Cutler TA, Ha J-H, Loh SN

Dynamic features of homodimer interfaces calculated by normal-mode analysis
Tsuchiya Y, Kinoshita K, Endo S, Wako H

Automated electron-density sampling reveals widespread conformational polymorphism in proteins
Lang PT, Ng H-L, Fraser JS, Corn JE, Echols N, Sales M, Holton JM, Alber T

Intrinsic dynamic properties of proteins

Side-chain entropy and packing in proteins
Bromberg S, Dill KA (1994)

Insights into the local residual entropy of proteins provided by NMR relaxation
Li ZG, Raychaudhuri S, Wand AJ

Integration of protein motions with molecular networks reveals different mechanisms for permanent and transient interactions
Bhardwaj N, Abyzov A, Clarke D, Shou C, Gerstein MB

Internal motion in protein crystal structures
Schmidt A, Lamzin VS (2010)

Solvent-induced lid opening in lipases: A molecular dynamics study
Rehm S, Trodler P, Pleuss J

Conserved tertiary couplings stabilize elements in the PDZ fold, leading to characteristic patterns of domain conformational flexibility
Ho BK, Agard DA

Osmolytes modulate conformational exchange in solvent-exposed regions of membrane proteins
Jimenez RHF, Do Cao M-A, Kim M, Cafisco DS

Folding and aggregation

Protein-folding dynamics – The diffusion-collision model and experimental-data
Karplus M, Weaver DL

Polymer principles and protein folding
Dill KA

Protein folding pathways and state transitions described by classical equations of motion of an elastic network model
Williams G, Toon AJ

Mannosylglycerate stabilizes staphylococcal nuclease with restriction of slow beta-sheet motions
Pais TM, Lamosa P, Matzapetakis M, Turner DL, Santos H

Increasing protein stability: Importance of Delta C-p and the denatured state
Fu H, Grimsley G, Scholtz JM, Pace CN

Potentially amyloidogenic conformational intermediates populate the unfolding landscape of transthyretin: Insights from molecular dynamics simulations
Rodrigues JR, Simoes CJV, Silva CG, Brito RMM

Increased aggregation propensity of IgG2 subclass over IgG1: Role of conformational changes and covalent character in isolated aggregates
Franey H, Brych SR, Kolvenbach CG, Rajan RS

Folding and binding cascades: Dynamic landscapes and population shifts
Kumar S, Ma BY, Tsai CJ Sinha N, Nussinov R

Multiple diverse ligands binding at a single protein site: A matter of pre-existing populations
Ma BY, Shatsky M, Wolfson HJ, Nussinov R

Counterbalance of ligand- and self-coupled motions characterizes multispecificity of ubiquitin
Dasgupta B, Nakamura H, Kinjo AR

Pre-existing soft modes of motion uniquely defined by native contact topology facilitate ligand binding to proteins
Meireles L, Gur M, Bakan A, Bahar I

The dynamical response of hen egg white lysozyme to the binding of a carbohydrate ligand
Moorman VR, Valentine KG, Wang AJ

A flexible docking scheme to explore the binding selectivity of PDZ domains
Gerek ZN, Ozkan SB

50th anniversary of the word "Allosteric"
Changeux J-P

Allostery and cooperativity revisited
Cui Q, Karplus M

Determination of network of residues that regulate allostery in protein families using sequence analysis
Dima RI, Thirumalai D

Domain motion and interdomain hot spots in a multidomain enzyme
Chuang G-Y, Mehra-Chaudhary R, Ngan C-H, Zerbe BS, Kozakov D, Vajda S, Beamer LJ

Osmolyte-induced conformational changes in the Hsp90 molecular chaperone
Street TO, Krukenberg KA, Rosgen J, Bolen DW, Agard DA

The pyruvate kinase model system, a cautionary tale for the use of osmolyte perturbations to support conformational equilibria in allostery
Fenton AW, Johnson TA, Holyoak T


Virtual Issue 6, February 12: Protein Annotation

Protein Function Annotation: The next Frontier in Molecular Biology

Protein folding has been called the “major unsolved challenge” in understanding proteins. But, one could argue that the real challenge involves understanding, in molecular detail, what those proteins actually do—their detailed molecular function. In 2006, Protein Science published the results from the first Automated Function Prediction meeting, held in Detroit, MI, in 2005. Since then, protein function prediction has become a field in its own right, with researchers trying to make sense of the masses of proteins of unknown function, whose sequences and structures are determined by today’s high-throughput techniques. This virtual issue of Protein Science highlights some of the important articles published at that first AFP meeting, as well as more recently published articles in this relatively young, but exciting, area of protein science.

Introduction to the Virtual Issue
Jacquelyn S. Fetrow

Recent Articles- General Protein Function Prediction

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation
A. D. Wilkins, R. Lua, S. Erdin, R. M. Ward and O. Lichtarge

Toward prediction of functional protein pockets using blind docking and pocket search algorithms
Csaba Hetényi and David van der Spoel

Prediction of ligand-binding sites of proteins by molecular docking calculation for a random ligand library
Yoshifumi Fukunishi and Haruki Nakamura

Recent Articles- Function Prediction in A Specific Protein or Protein Family

Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains
Libusha Kelly, Hisayo Fukushima, Rachel Karchin, Jason M. Gow, Leslie W. Chinn, Ursula Pieper, Mark R. Segal, Deanna L. Kroetz and Andrej Sali

Fast and automated functional classification with MED-SuMo: An application on purine-binding proteins
Olivia Doppelt-Azeroual, François Delfaud, Fabrice Moriaud and Alexandre G. de Brevern

Analysis and prediction of calcium-binding pockets from apo-protein structures exhibiting calcium-induced localized conformational changes
Xue Wang, Kun Zhao, Michael Kirberger, Hing Wong, Guantao Chen and Jenny J. Yang

Recent Articles- Examples of Why Protein Function Prediction Is So Hard

Predicting memapsin 2 (β-secretase) hydrolytic activity
Xiaoman Li, Huang Bo, Xuejun C. Zhang, Jean A. Hartsuck and Jordan Tang

Comparison of human solute carriers
Avner Schlessinger, Pär Matsson, James E. Shima, Ursula Pieper, Sook Wah Yee, Libusha Kelly, Leonard Apeltsin, Robert M. Stroud, Thomas E. Ferrin, Kathleen M. Giacomini and Andrej Sali

Analysis of the plasticity of location of the Arg244 positive charge within the active site of the TEM-1 β-lactamase
David C. Marciano, Nicholas G. Brown and Timothy Palzkill

Comparative surface geometry of the protein kinase family
Elaine E. Thompson, Alexandr P. Kornev, Natarajan Kannan, Choel Kim, Lynn F. Ten Eyck and Susan S. Taylor

Future of Function Prediction Is Functional Site Design

Motif-directed flexible backbone design of functional interactions
James J. Havranek and David Baker

From the First Automated Protein Function Prediction (AFP) Meeting in 2005

New avenues in protein function prediction
Iddo Friedberg, Martin Jambon and Adam Godzik

Recurrent use of evolutionary importance for functional annotation of proteins based on local structural similarity
David M. Kristensen, Brian Y. Chen, Viacheslav Y. Fofanov, R. Matthew Ward, Andreas Martin Lisewski, Marek Kimmel, Lydia E. Kavraki and Olivier Lichtarge

Structure-based function inference using protein family-specific fingerprints
Deepak Bandyopadhyay, Jun Huan, Jinze Liu, Jan Prins, Jack Snoeyink, Wei Wang and Alexander Tropsha

A categorization approach to automated ontological function annotation
Karin Verspoor, Judith Cohn, Susan Mniszewski and Cliff Joslyn

Enhanced automated function prediction using distantly related sequences and contextual association by PFP
Troy Hawkins, Stanislav Luban and Daisuke Kihara

Functional annotation prediction: All for one and one for all
Ori Sasson, Noam Kaplan and Michal Linial


Virtual Issue 5, July 2011: Research Frontiers

Frontiers in Protein Research: A Joint Virtual Issue of Protein Science and PROTEINS: Structure, Function, and Bioinformatics

This virtual issue is the first joint venture between Protein Science and PROTEINS: STRUCTURE, FUNCTION, AND BIOINFORMATICS. The collection of papers highlights current trends in the field. The issue is organized primarily around relatively new areas of protein research (e.g. unfolded proteins, membrane proteins, amyloids, interactions, design, binding), as represented by some highly cited papers in these journals in recent years. The collection certainly contrasts with the time when PROTEINS and Protein Science first appeared in 1986 and 1992, respectively. At that time few crystal structures were routine, only one high resolution membrane protein structure was available, and the VAX computer was king. Now we see papers on the high resolution structures of seemingly intractable amyloid fibers and giant complexes like the carboxysome, alongside microsecond simulations. Yet proteins continue to challenge us with their complexity and the papers in this virtual issue also underscore the need for continued studies of fundamental structural and physico-chemical properties of proteins.

Paramagnetic relaxation enhancements in unfolded proteins: Theory and application to drkN SH3 domain

Yi Xue, Ivan S. Podkorytov, D. Krishna Rao, Nathan Benjamin, Honglei Sun and Nikolai R. Skrynnikov

Order propensity of an intrinsically disordered protein, the cyclin-dependent-kinase inhibitor Sic1

Stefania Brocca, Mária Šamalíková, Vladimir N. Uversky, Marina Lotti, Marco Vanoni, Lilia Alberghina and Rita Grandori

Production of functional bacteriorhodopsin by an Escherichia coli cell-free protein synthesis system supplemented with steroid detergent and lipid

Kazumi Shimono, Mie Goto, Takashi Kikukawa, Seiji Miyauchi, Mikako Shirouzu, Naoki Kamo and Shigeyuki Yokoyama

Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations

George Khelashvili, Alan Grossfield, Scott E. Feller, Michael C. Pitman and Harel Weinstein

Selected-fit versus induced-fit protein binding: Kinetic differences and mutational analysis

Thomas R. Weikl and Carola von Deuster

At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?

Shina C. L. Kamerlin and Arieh Warshel

A summary of the measured pK values of the ionizable groups in folded proteins

Gerald R. Grimsley, J. Martin Scholtz and C. Nick Pace

Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process

Jed J. W. Wiltzius, Stuart A. Sievers, Michael R. Sawaya and David Eisenberg

Thermodynamics and dynamics of amyloid peptide oligomerization are sequence dependent

Yan Lu, Philippe Derreumaux, Zhi Guo, Normand Mousseau and Guanghong Wei

Improved prediction of protein side-chain conformations with SCWRL4

Georgii G. Krivov, Maxim V. Shapovalov and Roland L. Dunbrack Jr.

Engineered cystine knot peptides that bind αvβ3, αvβ5, and α5β1 integrins with low-nanomolar affinity

Richard H. Kimura, Aron M. Levin, Frank V. Cochran and Jennifer R. Cochran

RosettaHoles: Rapid assessment of protein core packing for structure prediction, refinement, design, and validation

Will Sheffler and David Baker

An all-atom structure-based potential for proteins: Bridging minimal models with all-atom empirical forcefields

Paul C. Whitford, Jeffrey K. Noel, Shachi Gosavi, Alexander Schug, Kevin Y. Sanbonmatsu and José N. Onuchic

Microsecond simulations of the folding/unfolding thermodynamics of the Trp-cage miniprotein

Ryan Day, Dietmar Paschek and Angel E. Garcia

Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures

Paul Labute

Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens function

Arthur Laganowsky, Justin L. P. Benesch, Meytal Landau, Linlin Ding, Michael R. Sawaya, Duilio Cascio, Qingling Huang, Carol V. Robinson, Joseph Horwitz and David Eisenberg

Small-angle scattering for structural biology—Expanding the frontier while avoiding the pitfalls

David A. Jacques and Jill Trewhella

Insights from multiple structures of the shell proteins from the β-carboxysome

Shiho Tanaka, Michael R. Sawaya, Martin Phillips and Todd O. Yeates



Virtual Issue 4, May 2011: Pacific Rim

Focus on The Pacific Rim

This issue highlights recent contributions to Protein Science from the nations of the Pacific Rim and the Asian Pacific Protein Association (APPA). Protein science is a vibrant and thriving discipline in all of these countries and, while it is clearly impossible to provide a compressive overview, this issue offers a taste of the exciting and diverse research being undertaken. Three comprehensive, up-to-date, review articles on protein stabilization by small molecules, cryo-electron microscopy, and small angle X-ray scattering are included together with eleven original articles. These papers span the range from protein design, protein folding and stability, enzymology, structural biology, and membrane proteins. This issue is particularly timely since it coincides with the recent 3th international Asian Pacific Protein Association conference held in Shanghai which was jointly sponsored by the APPA and The Protein Society.

Introduction to the virtual issue
Daniel Raleigh

Small-angle scattering for structural biology—Expanding the frontier while avoiding the pitfalls
David A. Jacques and Jill Trewhella

Rapid exploration of the folding topology of helical membrane proteins using paramagnetic perturbation
Kwon Joo Yeo, Hye-Yeon Kim, Young Pil Kim, Eunha Hwang, Myung Hee Kim, Chaejoon Cheong, Senyon Choe and Young Ho Jeon

Supachai Sakkhachornphop, Supat Jiranusornkul, Kanchanok Kodchakorn, Sawitree Nangola, Thira Sirisanthana and Chatchai Tayapiwatana

Crystal structure of the human receptor activity-modifying protein 1 extracellular domain
Seisuke Kusano, Mutsuko Kukimoto-Niino, Ryogo Akasaka, Mitsutoshi Toyama, Takaho Terada, Mikako Shirouzu, Takayuki Shindo and Shigeyuki Yokoyama

Structural physiology based on electron crystallography
Yoshinori Fujiyoshi

Structural basis for the negative regulation of bacterial stress response by RseB
Dong Young Kim, Eunju Kwon, JongKeun Choi, Hye-Yeon Hwang and Kyeong Kyu Kim

Structural insight into the catalytic mechanism of gluconate 5-dehydrogenase from Streptococcus suis: Crystal structures of the substrate-free and quaternary complex enzymes
Qiangmin Zhang, Hao Peng, Feng Gao, Yiwei Liu, Hao Cheng, John Thompson and George F. Gao

Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin
Yong-Gang Chang, Ai-Xin Song, Yong-Guang Gao, Yan-Hong Shi, Xiao-Jing Lin, Xue-Tao Cao, Dong-Hai Lin and Hong-Yu Hu

NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35
Reema Alag, Insaf A. Qureshi, Nagakumar Bharatham, Joon Shin, Julien Lescar and Ho Sup Yoon

Identification of transient hub proteins and the possible structural basis for their multiple interactions
Miho Higurashi, Takashi Ishida and Kengo Kinoshita

Lone pair ••• π interactions between water oxygens and aromatic residues: Quantum chemical studies based on high-resolution protein structures and model compounds
Alok Jain, Venkatnarayan Ramanathan and Ramasubbu Sankararamakrishnan

Stereoelectronic effects on the transition barrier of polyproline conformational interconversion
Yi-Chun Chiang, Yu-Ju Lin and Jia-Cherng Horng

Counting peptide-water hydrogen bonds in unfolded proteins
Haipeng Gong, Lauren L. Porter and George D. Rose

Effect of trehalose on protein structure
Nishant Kumar Jain and Ipsita Roy



Virtual Issue 3, July 2010: Protein Folding

Protein Folding: Short Question – Long Answer

Arguably, more articles in Protein Science deal with the folding of proteins than any other subject. Solving the protein folding problem also remains as one of the major challenges in biology. This Virtual Issue combines two groups of articles from Protein Science that deal with this subject. The first selections have already established themselves as “citation classics”. The second group of selections includes articles published within the past three years that can be characterized as “up-and-coming citation classics”. Together, these contributions revisit established highlights and provide pointers to future developments.

Introduction to the virtual issue
Brian W. Matthews

Principles of protein folding-A perspective from simple exact models
Ken A. Dill, Sarina Bromberg, Kaizhi Yue, Hue Sun Chan, Klaus M. Ftebig, David P. Yee and Paul D. Thomas

Structure and dynamics of de novo proteins from a designed superfamily of 4-helix bundles
Abigail Go, Seho Kim, Jean Baum and Michael H. Hecht

Molecular dynamics simulations of alanine rich β-sheet oligomers: Insight into amyloid formation
Buyong Ma, Ruth Nussinov

Denaturant m values and heat capacity changes: Relation to changes in accessible surface areas of protein unfolding
Jeffrey K. Myers, C. Nick Pace and J. Martin Scholtz

Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions
Avijit Chakrabartty, Tanja Kortemme and Robert L. Baldwin

Toward quantification of protein backbone-backbone hydrogen bonding energies: An energetic analysis of an amide-to-ester mutation in an α-helix within a protein
Jianmin Gao and Jeffery W. Kelly

Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction
Hongyi Zhou and Yaoqi Zhou

The effects of macromolecular crowding on the mechanical stability of protein molecules
Jian-Min Yuan, Chia-Lin Chyan, Huan-Xiang Zhou, Tse-Yu Chung, Haibo Peng, Guanghui Ping and Guoliang Yang

Contact order revisited: Influence of protein size on the folding rate
Dmitry N. Ivankov, Sergiy O. Garbuzynskiy, Eric Alm, Kevin W. Plaxco, David Baker, Alexei V. Finkelstein

The topomer search model: A simple, quantitative theory of two-state protein folding kinetics
Dmitrii E. Makarov, Kevin W. Plaxco

Folding thermodynamics and kinetics of the leucine-rich repeat domain of the virulence factor Internalin B
Naomi Courtemanche, Doug Barrick

Structural characterization of partially folded intermediates of apomyoglobin H64F
Stephan Schwarzinger, Ronaldo Mohana-Borges, Gerard J.A. Kroon, H. Jane Dyson, Peter E. Wright

3D domain swapping: A mechanism for oligomer assembly
Melanie J. Bennett, Michael P. Schlunegger, David Eisenberg

RosettaHoles: Rapid assessment of protein core packing for structure prediction, refinement, design, and validation
Will Sheffler, David Baker

GroEL-mediated protein folding
Wayne A. Fenton, Arthur L. Horwich

The Brichos domain of prosurfactant protein C can hold and fold a transmembrane segment
Hanna Johansson, Maria Eriksson, Kerstin Nordling, Jenny Presto, Jan Johansson

Export chaperone SecB uses one surface of interaction for diverse unfolded polypeptide ligands
Angela A. Lilly, Jennine M. Crane, Linda L. Randall

Escherichia coli maltose-binding protein is uncommonly effective at promoting the solubility of polypeptides to which it is fused
Rachel B. Kapust, David S. Waugh

Deamidation destabilizes and triggers aggregation of a lens protein, βA3-crystallin
Takumi Takata, Julie T. Oxford, Borries Demeler, Kirsten J. Lampi

Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens function
Arthur Laganowsky, Justin L. P. Benesch, Meytal Landau, Linlin Ding, Michael R. Sawaya, Duilio Cascio, Qingling Huang, Carol V. Robinson, Joseph Horwitz, David Eisenberg


Virtual Issue 2, November 2009: Learning about Proteins

Learning About Proteins That Live in Membranes

Protein Science
began publishing in 1992, not long after we were treated to the first high-resolution membrane protein structure. The photosynthetic reaction center structure finally showed that membrane proteins could be investigated at the atomic level, which induced a ratcheting up of membrane protein work that continues to build steam. Protein Science has been a natural place for reporting these efforts and this virtual issue highlights the breadth of membrane protein subjects that have found a home in the journal.

Introduction to the virtual issue
James U. Bowie

Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms
Erik Wallin, Gunnar Von Heijne

Toward genomic identification of beta-barrel membrane proteins: composition and architecture of known structures
William C. Wimley

The progress of membrane protein structure determination
Stephen H. White

A limited universe of membrane protein families and folds
Amit Oberai, Yungok Ihm, Sanguk Kim, James U. Bowie

Structure of the membrane channel porin from Rhodopseudomonas blastica at 2.0 Å resolution
A. Kreusch, A. Neubüser, E. Schiltz, J. Weckesser, G.E. Schulz

Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA
Andrew D. Ferguson, James W. Coulton, Kay Diederichs, Wolfram Welte, Volkmar Braun, Hans-Peter Fiedler

Structure and electrostatic property of cytoplasmic domain of ZntB transporter
Kemin Tan, Alicia Sather, Janice L. Robertson, Shiu Moy, Benoît Roux, Andrzej Joachimiak

Simultaneous assignment and structure determination of a membrane protein from NMR orientational restraints
Francesca M. Marassi, Stanley J. Opella

Rationalizing alpha-helical membrane protein crystallization
Simon Newstead, Sébastien Ferrandon, So Iwata

Best alpha-helical transmembrane protein topology predictions are achieved using hidden Markov models and evolutionary information
Håkan Viklund, Arne Elofsson

Experimentally based topology models for E. coli inner membrane proteins
Mikaela Rapp, David Drew, Daniel O. Daley, Johan Nilsson, Tiago Carvalho, Karin Melén, Jan-Willem De Gier, Gunnar Von Heijne

How do helix-helix interactions help determine the folds of membrane proteins? Perspectives from the study of homo-oligomeric helical bundles
William F. DeGrado, Holly Gratkowski, James D. Lear

Determination of membrane protein stability via thermodynamic coupling of folding to thiol-disulfide interchange
Lidia Cristian, James D. Lear, William F. DeGrado

Interaction and conformational dynamics of membrane-spanning protein helices
Dieter Langosch, Isaiah T. Arkin

An improved tripod amphiphile for membrane protein solubilization
Seungju M. Yu, D. Tyler McQuade, Mariah A. Quinn, Christian P.R. Hackenberger, Samuel H. Gellman, Mark P. Krebs, Arthur S. Polans

Self-assembly of single integral membrane proteins into soluble nanoscale phospholipid bilayers
Timothy H. Bayburt, Stephen G. Sligar

Engineering a G protein-coupled receptor for structural studies: stabilization of the BLT1 receptor ground state
Aimée Martin, Marjorie Damian, Michel Laguerre, Joseph Parello, Bernard Pucci, Laurence Serre, Sophie Mary, Jacky Marie, Jean-Louis Banères

Expression of human peripheral cannabinoid receptor for structural studies
Alexei A. Yeliseev, Karen K. Wong, Olivier Soubias, Klaus Gawrisch

Efficient production of membrane-integrated and detergent-soluble G protein-coupled receptors in Escherichia coli
A. James Link, Georgios Skretas, Eva-Maria Strauch, Nandini S. Chari, George Georgiou

Genetic selection system for improving recombinant membrane protein expression in E. coli
Elizabeth Massey-Gendel, Anni Zhao, Gabriella Boulting, Hye-Yeon Kim, Michael A. Balamotis, Len M. Seligman, Robert K. Nakamoto, James U. Bowie



Virtual Issue 1, May 2009: Structure of Myoglobin

Celebrating The Structure of Myoglobin and Its Impact on the Science of Proteins

This virtual issue of Protein Science is intended to commemorate the 50th anniversary of the myoglobin structure determination. It is made up of articles selected exclusively from the first six years of the journal’s publication (1992-1997). As such, the coverage is not all-inclusive. Nevertheless, it does provide a remarkable historical overview not only of the myoglobin structure determination, per se, but other pioneers who have shaped the field of protein science as we now understand it. Against all odds, Perutz and Kendrew established the field of protein crystallography. The structure of myoglobin, now 50 years ago, vindicated their efforts. More important, however, was the revolution in structural biology that they made possible. This volume celebrates their achievement.

A message from the editor
Brian W. Matthews

A little ancient history
Richard E. Dickerson

The beginnings of structural biology
Michael G. Rossmann

Max Perutz's achievements: How did he do it?
David Eisenberg

Obituary: Sir John Kendrew (1917-1997)
M.F. Perutz

Linderstrøm-Lang and the Carlsberg Laboratory: The view of a postdoctoral fellow in 1954
Frederic M. Richards

How my interest in proteins developed
Linus Pauling

Memories of early days in protein science, 1926-1940
John T. Edsall

Charles Tanford

Poly-α-amino acids as the simplest protein models: Recollections of a retired state president
Ephraim Katchalski-Katzir

The contributions of Stein and Moore to protein science
James M. Manning

Christian B. Anfinsen (1916-1995) Remembering His Life and His Science
Michael Young

Some early tracer experiments with stable isotopes
Mildred Cohn

ATP and inorganic pyro- and polyphosphate
Arthur Kornberg

The joys and vicissitudes of protein science
Daniel E. Koshland Jr.

The chemical synthesis of proteins
Bruce Merrifield

Reconstructing history with amino acid sequences
Russell F. Doolittle

A database of protein structure families with common folding motifs
Liisa Holm, Christos Ouzounis, Chris Sander, Georg Tuparev, Gert Vriend

The molten globule intermediate of apomyoglobin and the process of protein folding
Doug Barrick, Robert L. Baldwin

Principles of protein folding - A perspective from simple exact models
Ken A. Dill, Sarina Bromberg, Kaizhi Yue, Hue Sun Chan, Klaus M. Ftebig, David P. Yee, Paul D. Thomas

Buried waters and internal cavities in monomeric proteins
Mark A. Williams, Julia M. Goodfellow, Janet M. Thornton

Sequence determinants of the capping box, a stabilizing motif at the N-termini of α-helices
Jeffrey W. Seale, Rajgopal Srinivasan, George D. Rose

De novo design of the hydrophobic cores of proteins
John R. Desjarlais, Tracy M. Handel

3D domain swapping: A mechanism for oligomer assembly
Melanie J. Bennett, Michael P. Schlunegger, David Eisenberg

Influenza virus neuraminidase: Structure, antibodies, and inhibitors
P.M. Colman