BIOPHYSICAL THEORY AND MODELING |
Folding and Misfolding of the Collagen Triple Helix: Markov Analysis of Molecular Dynamics Simulations
Sanghyun Park 1, Teri E Klein 1 and Vijay S Pande 1*
1 Stanford University
* To whom correspondence should be addressed. E-mail: pande{at}stanford.edu.
Submitted on March 5, 2007
Revised on April 15, 2007
Accepted on 29 June 2007
 |
Abstract |
|---|
Folding and misfolding of the collagen triple helix are studied through molecular dynamics simulations of two collagen-like peptides, [(POG)10]3 and [(POG)4POA(POG)5]3, which are models for wild-type and mutant collagen respectively. In order to extract long time dynamics from short trajectories, we employ Markov state models. By analyzing thermodynamic and kinetic quantities calculated from the Markov state models, we examine folding mechanisms of the collagen triple helix and consequences of glycine mutations. We find that the C-to-N zipping of the collagen triple helix must be initiated by a nucleation event consisting of formation of three stable hydrogen bonds, and that zipping through a glycine mutation site requires a re-nucleation event which also consists of formation of three stable hydrogen bonds. Our results also suggest that slow kinetics, rather than free energy differences, is mainly responsible for the stability of the collagen triple helix.
Key Words:
collagen, distributed computing, markov model, misfolding disease, molecular dynamics, protein folding
