MD-TASK: a software suite for analyzing molecular dynamics trajectories

Abstract

SummaryMolecular dynamics (MD) determines the physical motions of atoms of a biological macromolecule in a cell-like environment and is an important method in structural bioinformatics. Traditionally, measurements such as root mean square deviation, root mean square fluctuation, radius of gyration, and various energy measures have been used to analyze MD simulations. Here, we present MD-TASK, a novel software suite that employs graph theory techniques, perturbation response scanning, and dynamic cross-correlation to provide unique ways for analyzing MD trajectories.Availability and implementationMD-TASK has been open-sourced and is available for download from https://github.com/RUBi-ZA/MD-TASK, implemented in Python and supported on Linux/Unix.

Modulation of Human Hsp90α Conformational Dynamics by Allosteric Ligand Interaction at the C-Terminal Domain

“…Dynamic residue networks (DRNs) 47 Starting with ΔL i (Figure 6B), it is evident that ligand binding leads to an increase in L i , particularly at the NTDs of both protomers (~1 unit), with the largest increase observed for residues belonging to ATP-lid (residues 130-160). This observation is notably accentuated in protomer B of the SANC309 complex, with ΔL i values >3.0.…”

Allosteric Modulation of Conformational Dynamics in Human Hsp90α: A Computational Study

“…DCC is calculated based on the reduction and normalization of the 3N x 3N covariance matrix (C). The MD-TASK (Brown et al, 2017a) software suite was used to calculate DCC for each MD trajectory. C is constructed from the MD trajectory sampling data at 100 ps intervals, and the average deviation of each C α atom from a mean structure representative of the trajectory length is calculated.…”

“…To analyse inter-and intra-domain communication, the protein is represented as a residue interaction network (RIN), where the C β atoms of each residue (C α for glycine) are treated as nodes within the network, and edges between nodes defined within a distance cut off of 6.7 Å (Atilgan et al, 2004). In this study, the MD-TASK (Brown et al, 2017a) software suite is used to construct dynamic RINs (DRN) based on the all-atom MD trajectories. Each DRN is the combination of RINs representative of time points (frames) in the MD trajectory, using a 200 ps time interval between frames.…”

“…Finally, MD-TASK averages the ΔL i and BC matrices. Average ΔL i and BC indicates residues that experience permanent changes in ΔL i and BC as opposed to minor fluctuations over the course of the MD trajectory (Brown et al, 2017a). For comparative purposes, BC values are normalized in the range 0.0 -1.0.…”

“…Perturbation response scanning (PRS) is a computational technique used to predict the relative response of all residues in a protein, to an external force perturbation, such as ligand binding, at a single residue. The theory of PRS has been thoroughly described in previous studies (Atilgan & (1) Atilgan, 2009;Atilgan et al, 2010;Penkler et al, 2017); the algorithm is available in the MD-TASK software suite (Brown et al, 2017a). In brief, PRS utilizes linear response theory (LRT) to approximate the shift in coordinates (R 1 ) of a given protein conformation (R 0 ) in response to a perturbation of the Hamiltonian (Yilmaz & Atilgan, 2000;Ikeguchi et al, 2005;Atilgan & Atilgan, 2009).…”