title: Stochastic Resonance in Protein Folding Dynamics.
abstract: Although protein folding reactions are usually studied under static external conditions, it is likely that proteins fold in a locally fluctuating cellular environment in vivo. To mimic such behavior in in vitro experiments, the local temperature of the solvent can be modulated either harmonically or using correlated noise. In this study, coarse-grained molecular simulations are used to investigate these possibilities, and it is found that both periodic and correlated random fluctuations of the environment can indeed accelerate folding kinetics if the characteristic frequencies of the applied fluctuations are commensurate with the internal timescale of the folding reaction; this is consistent with the phenomenon of stochastic resonance observed in many other condensed-matter processes. To test this theoretical prediction, the folding dynamics of phosphoglycerate kinase under harmonic temperature fluctuations are experimentally probed using Förster resonance energy transfer fluorescence measurements. To analyze these experiments, a combination of theoretical approaches is developed, including stochastic simulations of folding kinetics and an analytical mean-field kinetic theory. The experimental observations are consistent with the theoretical predictions of stochastic resonance in phosphoglycerate kinase folding. When combined with an alternative experiment on the protein VlsE using a power spectrum analysis, elaborated in Dave et al., ChemPhysChem 2016, 10.1002/cphc.201501041, the overall data overwhelmingly point to the experimental confirmation of stochastic resonance in protein folding dynamics.
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, Computation Institute, James Franck Institute, University of Chicago, Chicago, Illinois, 60637, USA.
authors.forename: Aram
authors.initials: A
authors.lastname: Davtyan
authors.affiliation: Department of Physics, Ariel University, Ariel, 40770, Israel.
authors.forename: Max
authors.initials: M
authors.lastname: Platkov
authors.affiliation: Department of Chemistry and Physics and, Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Gruebele
authors.affiliation: Department of Chemistry and Biochemistry and, Institute for Physical Science and Technology, University of Maryland, College Park, MD, 20742, USA. gpapoian@umd.edu.
authors.forename: Garegin A
authors.identifier: 0000-0001-8580-3790
authors.initials: GA
authors.lastname: Papoian
mesh_terms: D031541:Fluorescence Resonance Energy Transfer; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013269:Stochastic Processes
chemical_list: D011506:Proteins
keywords: Förster resonance energy transfer; brownian dynamics; molecular dynamics; protein folding; stochastic resonance