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Open Access Methodology article

Time-resolved force distribution analysis

Bogdan I Costescu1 and Frauke Gräter12*

Author Affiliations

1 Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany

2 CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China

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BMC Biophysics 2013, 6:5  doi:10.1186/2046-1682-6-5

Published: 1 May 2013

Abstract

Background

Biomolecules or other complex macromolecules undergo conformational transitions upon exposure to an external perturbation such as ligand binding or mechanical force. To follow fluctuations in pairwise forces between atoms or residues during such conformational changes as observed in Molecular Dynamics (MD) simulations, we developed Time-Resolved Force Distribution Analysis (TRFDA).

Results

The implementation focuses on computational efficiency and low-memory usage and, along with the wide range of output options, makes possible time series analysis of pairwise forces variation in long MD simulations and for large molecular systems. It also provides an exact decomposition of pairwise forces resulting from 3- and 4-body potentials and a unified treatment of pairwise forces between atoms or residues. As a proof of concept, we present a stress analysis during unfolding of ubiquitin in a force-clamp MD simulation.

Conclusions

TRFDA can be used, among others, in tracking signal propagation at atomic level, for characterizing dynamical intermolecular interactions (e.g. protein-ligand during flexible docking), in development of force fields and for following stress distribution during conformational changes.