Computational prediction of hinge axes in proteins

BMC Bioinformatics

Research

Rittika Shamsuddin¹  Sheila Jaswal²  Kathryn McMenimen³  Audrey Lee-St John³  Milka Doktorova⁴ 

[1] Computer Science, University of Texas, Dallas, TX, USA;Dept. of Chemistry, Amherst College, Amherst, MA, USA;Dept. of Computer Science and Dept. of Chemistry, Mount Holyoke College, South Hadley, MA, USA;Tri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medical College, New York, NY, USA;

关键词: protein flexibility;    rigidity theory;    linear algebra;   

DOI  :  10.1186/1471-2105-15-S8-S2

来源: Springer

【 摘 要 】

BackgroundA protein's function is determined by the wide range of motions exhibited by its 3D structure. However, current experimental techniques are not able to reliably provide the level of detail required for elucidating the exact mechanisms of protein motion essential for effective drug screening and design. Computational tools are instrumental in the study of the underlying structure-function relationship. We focus on a special type of proteins called "hinge proteins" which exhibit a motion that can be interpreted as a rotation of one domain relative to another.ResultsThis work proposes a computational approach that uses the geometric structure of a single conformation to predict the feasible motions of the protein and is founded in recent work from rigidity theory, an area of mathematics that studies flexibility properties of general structures. Given a single conformational state, our analysis predicts a relative axis of motion between two specified domains. We analyze a dataset of 19 structures known to exhibit this hinge-like behavior. For 15, the predicted axis is consistent with a motion to a second, known conformation. We present a detailed case study for three proteins whose dynamics have been well-studied in the literature: calmodulin, the LAO binding protein and the Bence-Jones protein.ConclusionsOur results show that incorporating rigidity-theoretic analyses can lead to effective computational methods for understanding hinge motions in macromolecules. This initial investigation is the first step towards a new tool for probing the structure-dynamics relationship in proteins.

【 授权许可】

Unknown   
© Shamsuddin et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.