title: A Maximum-Caliber Approach to Predicting Perturbed Folding Kinetics Due to Mutations.
abstract: 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 nontrivial protein folding systems for which non-native interactions play a significant role, including (1) tryptophan variants of the GB1 hairpin, (2) salt-bridge mutations of the Fs peptide helix, and (3) MSMs built from ultralong folding trajectories of FiP35 and GTT variants of the 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.
authors.affiliation: Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Voelz
mesh_terms: D000595:Amino Acid Sequence; D007700:Kinetics; D008390:Markov Chains; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000737:chemistry
chemical_list: D010455:Peptides; D014364:Tryptophan