Calculation of Enzyme Fluctuograms from All-Atom Molecular Dynamics Simulation

Abstract

In this work, a computational framework is presented to compute the time evolution of force constants for a coarse grained (CG) elastic network model along an all-atom molecular dynamics trajectory of a protein system. Obtained via matching distance fluctuations, these force constants represent strengths of mechanical coupling between CG beads. Variation of coupling strengths with time is hence termed the fluctuogram of protein dynamics. In addition to the schematic procedure and implementation considerations, several ways of combining force constants and data analysis are presented to illustrate the potential application of protein fluctuograms. The unique angle provided by the fluctuogram expands the scope of atomistic simulations and is expected to impact upon fundamental understanding of protein dynamics as well as protein engineering technologies.

Keywords: Elastic network model; Fluctuation matching; Fluctuogram; Multiscale coarse graining; Protein dynamics; Rat anionic trypsin; Serine protease.