Multidimensional umbrella sampling and replica-exchange molecular dynamics simulations for structure prediction of transmembrane helix dimers.

ABSTRACT: Structural information of a transmembrane (TM) helix dimer is useful in understanding molecular mechanisms of important biological phenomena such as signal transduction across the cell membrane. Here, we describe an umbrella sampling (US) scheme for predicting the structure of a TM helix dimer in implicit membrane using the interhelical crossing angle and the TM-TM relative rotation angles as the reaction coordinates. This scheme conducts an efficient conformational search on TM-TM contact interfaces, and its robustness is tested by predicting the structures of glycophorin A (GpA) and receptor tyrosine kinase EphA1 (EphA1) TM dimers. The nuclear magnetic resonance (NMR) structures of both proteins correspond to the global free-energy minimum states in their free-energy landscapes. In addit

SUBMITTER: Li PC 

PROVIDER: S-EPMC4083740 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature