%0 Journal Article
%T A minimal ligand binding pocket within a network of correlated mutations identified by multiple sequence and structural analysis of G protein coupled receptors
%A Subhodeep Moitra
%A Kalyan Tirupula
%A Judith Klein-Seetharaman
%A Chris Langmead
%J BMC Biophysics
%D 2012
%I BioMed Central
%R 10.1186/2046-1682-5-13
%X GREMLIN significantly enriches the edges containing residues that are part of the ligand binding pocket, when compared to a control distribution of edges drawn from a random graph. An analysis of these edges reveals a minimal GPCR binding pocket containing four residues (T1183.33, M2075.42, Y2686.51 and A2927.39). Additionally, of the ten residues predicted to have the most long-range interactions (A1173.32, A2726.55, E1133.28, H2115.46, S186EC2, A2927.39, E1223.37, G902.57, G1143.29 and M2075.42), nine are part of the ligand binding pocket.We demonstrate the use of GREMLIN to reveal a network of statistically correlated and functionally important residues in class A GPCRs. GREMLIN identified that ligand binding pocket residues are extensively correlated with distal residues. An analysis of the GREMLIN edges across multiple structures suggests that there may be a minimal binding pocket common to the seven known GPCRs. Further, the activation of rhodopsin involves these long-range interactions between extracellular and intracellular domain residues mediated by the retinal domain.
%K GPCR
%K GREMLIN
%K Long-range interactions
%K Ligand binding pocket
%K Graphical model
%U http://www.biomedcentral.com/2046-1682/5/13/abstract