High resolution mapping of protein motions in time and space with RMSX and Flipbook

Abstract

Abstract Demonstrating when and where proteins undergo conformational rearrangement remains challenging in molecular dynamics (MD) analysis, particularly for transient and localized motions. We introduce RMSX , a time-series extension of root-mean-square fluctuation (RMSF), and Flipbook , a general-purpose method for mapping simulation metrics onto structural, atomistic snapshots. Unlike traditional RMSF values, RMSX is performed over partitions of the original simulation – not its entirety. This simple extension allows RMSX to pinpoint not only the degree of fluctuation but also isolate when a significant motion takes place for any amino acid residue. Flipbook provides an engine for transforming time-series, residue-level data into salient, colored 3D structures. Flipbook can take in RMSX values, or other user-provided values, to see how they vary with time, coloring and scaling the amino acids according to those values. We demonstrate these tools’ utility on unbiased and steered MD simulations of ubiquitin, HIV-1 protease, and the bacterial adhesion protein SdrG. RMSX and Flipbook together form a streamlined, open-source suite for quantitative, high-resolution interrogation of biomolecular dynamics. RMSX and Flipbook are freely available at https://github.com/AntunesLab/rmsx .