Paper Citing NAMD - Abstract
Witt, Magdalena; Slusarz, Magdalena J.; Ciarkowski, Jerzy
Molecular modeling of Vasopressin V2 Receptor tetramer in hydrated lipid membrane
QSAR & COMBINATORIAL SCIENCE, 27:684-693, JUN 2008
Based on accessible experimental data we have constructed a model of Vasopressin V2 Receptor (V2R) tetramer in fully hydrated lipid membrane. To the best of our knowledge, this is the first Molecular Dynamics (MD) simulation of the tetramer model of a GPCR other than rhodopsin. The model consists of three inactive and one active V2R monomers. The activated unit is stabilized by Gs alpha (Ile(382)-Leu(394)) fragment and includes its natural ligand - vasopressin (AVP) docked. The pairs of neighboring protomers form contact dimers with the interface created by transmembrane helices TM3, TM4 of one partner and TM7, TM6 of the other. The between-dimers interface is composed by TM5 and TM4 of all monomers. Since experimental studies of GPCR oligomerization are not generally possible, there is a strong interest in using theoretical methods to predict their structure. Herein the NAnoscale Molecular Dynamics (NAMD) 2.6 package and CHARMm force field were used to conduct unconstrained MD calculations in periodic conditions. The optimal adjusting of monomers in lipid membrane surrounding was the purpose of simulation. Residues responsible for the oligomer stabilization were suggested and a compatibility of the whole model with available experimental data was discussed.
