Maciejewski, M, Barlow, PN and Tjandra, N (2014) Decoding the components of dynamics in three-domain proteins. Journal of Computational Chemistry, 35 (7). pp. 518-525. ISSN 01928651

Abstract

In this study, we examine the feasibility and limitations of describing the motional behavior of three-domain proteins in which the domains are linearly connected. In addition to attempting the determination of the internal and overall reorientational correlation times, we investigate the existence of correlations in the motions between the three domains. Since in linearly arranged three-domain proteins, there are typically no experimental data that can directly report on motional correlation between the first and the third domain, we address this question by dynamics simulations. Two limiting cases occur: (1) for weak repulsive potentials and (2) when strong repulsive potentials are applied between sequential domains. The motions of the terminal domains become correlated in the case of strong interdomain repulsive potentials when these potentials do not allow the angle between the sequential domains to be smaller than about 60degree. Using the model-free (MF) and extended MF formalisms of Lipari and Szabo, we find that the motional behavior can be separated into two components; the first component represents the concerted overall motion of the three domains, and the second describes the independent component of the motion of each individual domain. We find that this division of the motional behavior of the protein is maintained only when their timescales are distinct and can be made when the angles between sequential domains remain between 60degree and 160degree. In this work, we identify and quantify interdomain motional correlations. Copyright 2013 Wiley Periodicals, Inc

Item Type:	Article
Additional Information:	NIBR author: Maciejewski, M institute: NIBR contributor address: Center for Proteomic Chemistry, Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts, 02139.
Date Deposited:	13 Oct 2015 13:12
Last Modified:	04 Jul 2016 23:45
URI:	https://oak.novartis.com/id/eprint/22609