2016/05/25 by Vincent A. Voelz, Guangfeng Zhou, Voelz, Vincent A. +3 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Bacterial Genetics and Biotechnology #Biomolecules (q-bio.BM) #FOS: Biological sciences #FOS: Physical sciences #Protein Structure and Dynamics #RNA and protein synthesis mechanisms #Statistical Mechanics (cond-mat.stat-mech)
paper · pdf · doi:10.48550/arxiv.1605.07731
openalex publication_date 2016/05/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
We present a maximum-caliber method for inferring transition rates of a Markov State Model (MSM) with perturbed equilibrium populations, given estimates of state populations and rates for an unperturbed MSM. It is similar in spirit to previous approaches but given the inclusion of prior information it is more robust and simple to implement. We examine its performance in simple biased diffusion models of kinetics, and then apply the method to predicting changes in folding rates for several highly non-trivial protein folding systems for which non-native interactions play a significant role, including (1) tryptophan variants of GB1 hairpin, (2) salt-bridge mutations of Fs peptide helix, and (3) MSMs built from ultra-long folding trajectories of FiP35 and GTT variants of WW domain. In all cases, the method correctly predicts changes in folding rates, suggesting the wide applicability of maximum-caliber approaches to efficiently predict how mutations perturb protein conformational dynamics.