Open AccessUsing Kinetic Network Models To Probe Non-Native Salt-Bridge Effects on α-Helix Folding
Author(s) -
Guangfeng Zhou,
Vincent A. Voelz
Publication year - 2016
Publication title -
the journal of physical chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 392
eISSN - 1520-6106
pISSN - 1520-5207
DOI - 10.1021/acs.jpcb.5b11767
Subject(s) - salt bridge , folding (dsp implementation) , protein folding , markov chain , helix (gastropod) , native state , molecular dynamics , peptide , chemistry , phi value analysis , biophysics , computer science , biological system , crystallography , computational chemistry , biochemistry , biology , engineering , mutant , ecology , machine learning , snail , electrical engineering , gene
Salt-bridge interactions play an important role in stabilizing many protein structures, and have been shown to be designable features for protein design. In this work, we study the effects of non-native salt bridges on the folding of a soluble alanine-based peptide (Fs peptide) using extensive all-atom molecular dynamics simulations performed on the Folding@home distributed computing platform. Using Markov State Models, we show how non-native salt-bridges affect the folding kinetics of Fs peptide by perturbing specific conformational states. Furthermore, we present methods for the automatic detection and analysis of such states. These results provide insight into helix folding mechanisms and useful information to guide simulation-based computational protein design.