Prots: A fragment based protein thermo-stability potential
Article first published online: 5 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 80, Issue 1, pages 81–92, January 2012
How to Cite
Li, Y., Zhang, J., Tai, D., Russell Middaugh, C., Zhang, Y. and Fang, J. (2012), Prots: A fragment based protein thermo-stability potential. Proteins, 80: 81–92. doi: 10.1002/prot.23163
- Issue published online: 13 DEC 2011
- Article first published online: 5 OCT 2011
- Accepted manuscript online: 30 AUG 2011 10:49AM EST
- Manuscript Accepted: 31 JUL 2011
- Manuscript Revised: 18 JUL 2011
- Manuscript Received: 20 MAY 2011
- protein stability;
- thermostability potential
Designing proteins with enhanced thermo-stability has been a main focus of protein engineering because of its theoretical and practical significance. Despite extensive studies in the past years, a general strategy for stabilizing proteins still remains elusive. Thus effective and robust computational algorithms for designing thermo-stable proteins are in critical demand. Here we report PROTS, a sequential and structural four-residue fragment based protein thermo-stability potential. PROTS is derived from a nonredundant representative collection of thousands of thermophilic and mesophilic protein structures and a large set of point mutations with experimentally determined changes of melting temperatures. To the best of our knowledge, PROTS is the first protein stability predictor based on integrated analysis and mining of these two types of data. Besides conventional cross validation and blind testing, we introduce hypothetical reverse mutations as a means of testing the robustness of protein thermo-stability predictors. In all tests, PROTS demonstrates the ability to reliably predict mutation induced thermo-stability changes as well as classify thermophilic and mesophilic proteins. In addition, this white-box predictor allows easy interpretation of the factors that influence mutation induced protein stability changes at the residue level. Proteins 2012; © 2011 Wiley Periodicals, Inc.