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Issue 7, 2011
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Quantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of proteinligand interactions

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Abstract

In this article, we present a novel application of a quantum clustering (QC) technique to objectively cluster the conformations, sampled by molecular dynamics simulations performed on different ligand bound structures of the protein. We further portray each conformational population in terms of dynamically stable network parameters which beautifully capture the ligand induced variations in the ensemble in atomistic detail. The conformational populations thus identified by the QC method and verified by network parameters are evaluated for different ligand bound states of the protein pyrrolysyl-tRNA synthetase (DhPylRS) from D. hafniense. The ligand/environment induced re-distribution of protein conformational ensembles forms the basis for understanding several important biological phenomena such as allostery and enzyme catalysis. The atomistic level characterization of each population in the conformational ensemble in terms of the re-orchestrated networks of amino acids is a challenging problem, especially when the changes are minimal at the backbone level. Here we demonstrate that the QC method is sensitive to such subtle changes and is able to cluster MD snapshots which are similar at the side-chain interaction level. Although we have applied these methods on simulation trajectories of a modest time scale (20 ns each), we emphasize that our methodology provides a general approach towards an objective clustering of large-scale MD simulation data and may be applied to probe multistate equilibria at higher time scales, and to problems related to protein folding for any protein or proteinprotein/RNA/DNA complex of interest with a known structure.

Graphical abstract: Quantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of protein–ligand interactions

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Publication details

The article was received on 31 Jan 2011, accepted on 03 May 2011 and first published on 27 May 2011


Article type: Paper
DOI: 10.1039/C1MB05038A
Citation: Mol. BioSyst., 2011,7, 2320-2330
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    Quantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of proteinligand interactions

    M. Bhattacharyya and S. Vishveshwara, Mol. BioSyst., 2011, 7, 2320
    DOI: 10.1039/C1MB05038A

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