Paper Citing NAMD - Abstract
LeVine, Michael; Perez-Aguilar, Jose Manuel; Weinstein, Harel
N-body Information Theory (NbIT) Analysis of Rigid-Body Dynamics in Intracellular Loop 2 of the 5-HT2A Receptor
PROCEEDINGS IWBBIO 2014: INTERNATIONAL WORK-CONFERENCE ON BIOINFORMATICS AND BIOMEDICAL ENGINEERING, VOLS 1 AND 2, 1190-1201, 2014
Rigid-body motions of protein secondary structure are often implicated in mechanisms of protein function. In GPCRs, evidence suggests that intracellular loop 2 (IL2) contains a segment characterized as a helix when the activated receptor triggers downstream signaling. However, neither experimental nor computational methods are readily available to assess quantitatively the degree of collective motions in such secondary structure motifs of proteins. Here we describe a new element of our N-body Information Theory (NbIT) framework to address this problem. To this end we introduce total intercorrelation, a measure in information theory that can be used to describe n-body correlated dynamics between multivariate distributions, such as 3-dimensional atomic fluctuations in simulations of proteins. We also define two additional measures, the rigid-body fraction and correlation order, which can be determined from the decomposition of the configurational entropy. Using these measures, we analyze the dynamics of IL2 in microsecond Molecular Dynamics simulations of the 5-HT2A receptor to demonstrate the powerful features of the new analysis techniques in studying the collective motion dynamics of secondary structure motifs. The analysis reveals an intriguing difference in the extent of correlated motions in the helical segment of IL2 in the presence and absence of bound 5-HT, the endogenous agonist that activates the receptor and triggers downstream signaling, suggesting that IL2 rigid-body motions can display distinct behaviors that may discriminate functional mechanism of GPCRs.
