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A Local Rigid Body Framework for Global Optimization of Biomolecules

Kusumaatmaja, H.; Whittleston, C.S.; Wales, D.J.

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C.S. Whittleston

D.J. Wales


We present a local rigid body framework for simulations of biomolecules. In this framework, arbritrary sets of atoms may be treated as rigid bodies. Such groupings reduce the number of degrees of freedom, which can result in a significant reduction of computational time. As benchmarks, we consider global optimization for the tryptophan zipper (trpzip 1, 1LE0; using the CHARMM force field) and chignolin (1UAO; using the AMBER force field). We use a basin-hopping algorithm to find the global minima and compute the mean first encounter time from random starting configurations with and without the local rigid body framework. Minimal groupings are used, where only peptide bonds, termini, and side chain rings are considered rigid. Finding the global minimum is 4.2 and 2.5 times faster, respectively, for trpzip 1 and chignolin, within the local rigid body framework. We further compare O(105) low-lying local minima to the fully relaxed unconstrained representation for trpzip 1 at different levels of rigidification. The resulting Pearson correlation coefficients, and thus the apparent intrinsic rigidity of the various groups, appear in the following order: side chain rings > termini > trigonal planar centers ≥ peptide bonds side chains. This approach is likely to be even more beneficial for structure prediction in larger biomolecules.


Kusumaatmaja, H., Whittleston, C., & Wales, D. (2012). A Local Rigid Body Framework for Global Optimization of Biomolecules. Journal of Chemical Theory and Computation, 8(12), 5159-5165.

Journal Article Type Article
Publication Date Dec 11, 2012
Deposit Date May 22, 2013
Publicly Available Date Apr 24, 2014
Journal Journal of Chemical Theory and Computation
Print ISSN 1549-9618
Electronic ISSN 1549-9626
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 8
Issue 12
Pages 5159-5165


Accepted Journal Article (2.9 Mb)

Copyright Statement
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see

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