2026-04-17T03:45:14Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1024682025-12-04T21:15:23Zcom_2072_1057col_2072_478781col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Orellana, Laura author Yoluk, Ozge author Carrillo, Oliver author Orozco López, Modesto author Lindhal, Erik author 2016-10-07T15:03:06Z 2016-10-07T15:03:06Z 2016-08-31 2016-10-07T15:03:11Z 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 also show that the explored non-linear routes can delimit the lowest energy passages between end-states sampled by atomistic molecular dynamics. The integrative methodology presented here provides a powerful framework to extract and expand dynamic pathway information from the Protein Data Bank, as well as to validate sampling methods in general. Models moleculars Biofísica Proteïnes Molecular models Biophysics Proteins Prediction and validation of protein intermediate states from structurally rich ensembles and coarse grained simulations