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Motional timescale predictions by molecular dynamics simulations: Case study using proline and hydroxyproline sidechain dynamics.

Aliev, AE; Kulke, M; Khaneja, HS; Chudasama, V; Sheppard, TD; Lanigan, RM; (2014) Motional timescale predictions by molecular dynamics simulations: Case study using proline and hydroxyproline sidechain dynamics. Proteins , 82 (2) pp. 195-215. 10.1002/prot.24350. Green open access

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Abstract

We propose a new approach for force field optimisations which aims at reproducing dynamics characteristics using biomolecular MD simulations, in addition to improved prediction of motionally averaged structural properties available from experiment. As the source of experimental data for dynamics fittings, we use (13) C NMR spin-lattice relaxation times T1 of backbone and sidechain carbons, which allow to determine correlation times of both overall molecular and intramolecular motions. For structural fittings, we use motionally averaged experimental values of NMR J couplings. The proline residue and its derivative 4-hydroxyproline with relatively simple cyclic structure and sidechain dynamics were chosen for the assessment of the new approach in this work. Initially, grid search and simplexed MD simulations identified large number of parameter sets which fit equally well experimental J couplings. Using the Arrhenius-type relationship between the force constant and the correlation time, the available MD data for a series of parameter sets were analyzed to predict the value of the force constant that best reproduces experimental timescale of the sidechain dynamics. Verification of the new force-field parameters against NMR J couplings and correlation times showed consistent and significant improvements compared to the original force field in reproducing both structural and dynamics properties. The results suggest that matching experimental timescales of motions together with motionally averaged characteristics is the valid approach for force field parameter optimisation. Such a comprehensive approach is not restricted to cyclic residues and can be extended to other amino acid residues, as well as to the backbone. © Proteins 2013;. © 2013 Wiley Periodicals, Inc.

Type: Article
Title: Motional timescale predictions by molecular dynamics simulations: Case study using proline and hydroxyproline sidechain dynamics.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/prot.24350
Publisher version: http://dx.doi.org/10.1002/prot.24350
Additional information: © 2013 The Authors. Proteins published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: NMR, biomolecular force field, conformational analysis, molecular dynamics simulations, peptides, proline, proteins, structure
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: http://discovery.ucl.ac.uk/id/eprint/1399676
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