Prediction and validation of protein intermediate states from structurally rich ensembles and coarse-grained simulations.

ABSTRACT: Protein conformational changes are at the heart of cell functions, from signalling to ion transport. However, the transient nature of the intermediates along transition pathways hampers their experimental detection, making the underlying mechanisms elusive. Here we retrieve dynamic information on the actual transition routes from principal component analysis (PCA) of structurally-rich ensembles and, in combination with coarse-grained simulations, explore the conformational landscapes of five well-studied proteins. Modelling them as elastic networks in a hybrid elastic-network Brownian dynamics simulation (eBDIMS), we generate trajectories connecting stable end-states that spontaneously sample the crystallographic motions, predicting the structures of known intermediates along the paths. We

SUBMITTER: Orellana L 

PROVIDER: S-EPMC5013691 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature