Issue 5, 2016

Spatiotemporal multistage consensus clustering in molecular dynamics studies of large proteins

Abstract

The aim of this work is to find semi-rigid domains within large proteins as reference structures for fitting molecular dynamics trajectories. We propose an algorithm, multistage consensus clustering, MCC, based on minimum variation of distances between pairs of Cα-atoms as target function. The whole dataset (trajectory) is split into sub-segments. For a given sub-segment, spatial clustering is repeatedly started from different random seeds, and we adopt the specific spatial clustering with minimum target function: the process described so far is stage 1 of MCC. Then, in stage 2, the results of spatial clustering are consolidated, to arrive at domains stable over the whole dataset. We found that MCC is robust regarding the choice of parameters and yields relevant information on functional domains of the major histocompatibility complex (MHC) studied in this paper: the α-helices and β-floor of the protein (MHC) proved to be most flexible and did not contribute to clusters of significant size. Three alleles of the MHC, each in complex with ABCD3 peptide and LC13 T-cell receptor (TCR), yielded different patterns of motion. Those alleles causing immunological allo-reactions showed distinct correlations of motion between parts of the peptide, the binding cleft and the complementary determining regions (CDR)-loops of the TCR. Multistage consensus clustering reflected functional differences between MHC alleles and yields a methodological basis to increase sensitivity of functional analyses of bio-molecules. Due to the generality of approach, MCC is prone to lend itself as a potent tool also for the analysis of other kinds of big data.

Graphical abstract: Spatiotemporal multistage consensus clustering in molecular dynamics studies of large proteins

Supplementary files

Article information

Article type
Paper
Submitted
16 Dec 2015
Accepted
04 Mar 2016
First published
15 Mar 2016

Mol. BioSyst., 2016,12, 1600-1614

Author version available

Spatiotemporal multistage consensus clustering in molecular dynamics studies of large proteins

M. Kenn, R. Ribarics, N. Ilieva, M. Cibena, R. Karch and W. Schreiner, Mol. BioSyst., 2016, 12, 1600 DOI: 10.1039/C5MB00879D

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