Julian Lee and Dongseon Lee contributed equally to this work.
Protein loop modeling by using fragment assembly and analytical loop closure
Article first published online: 24 SEP 2010
Copyright © 2010 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 78, Issue 16, pages 3428–3436, December 2010
How to Cite
Lee, J., Lee, D., Park, H., Coutsias, E. A. and Seok, C. (2010), Protein loop modeling by using fragment assembly and analytical loop closure. Proteins, 78: 3428–3436. doi: 10.1002/prot.22849
- Issue published online: 8 NOV 2010
- Article first published online: 24 SEP 2010
- Accepted manuscript online: 17 AUG 2010 12:00AM EST
- Manuscript Accepted: 31 JUL 2010
- Manuscript Revised: 16 JUL 2010
- Manuscript Received: 19 MAY 2010
- MEST. Grant Number: Mid-career Researcher Program No. 2010-0000220
- NIH-NIGMS. Grant Numbers: R01-GM081710, R01-GM090205
- loop modeling;
- protein structure prediction;
- fragment assembly method;
- analytical loop closure;
- loop ensemble
Protein loops are often involved in important biological functions such as molecular recognition, signal transduction, or enzymatic action. The three dimensional structures of loops can provide essential information for understanding molecular mechanisms behind protein functions. In this article, we develop a novel method for protein loop modeling, where the loop conformations are generated by fragment assembly and analytical loop closure. The fragment assembly method reduces the conformational space drastically, and the analytical loop closure method finds the geometrically consistent loop conformations efficiently. We also derive an analytic formula for the gradient of any analytical function of dihedral angles in the space of closed loops. The gradient can be used to optimize various restraints derived from experiments or databases, for example restraints for preferential interactions between specific residues or for preferred backbone angles. We demonstrate that the current loop modeling method outperforms previous methods that employ residue-based torsion angle maps or different loop closure strategies when tested on two sets of loop targets of lengths ranging from 4 to 12. Proteins 2010. © 2010 Wiley-Liss, Inc.