Protein conformational plasticity and complex ligand-binding kinetics explored by atomistic simulations and Markov models.

ABSTRACT: Understanding the structural mechanisms of protein-ligand binding and their dependence on protein sequence and conformation is of fundamental importance for biomedical research. Here we investigate the interplay of conformational change and ligand-binding kinetics for the serine protease Trypsin and its competitive inhibitor Benzamidine with an extensive set of 150 μs molecular dynamics simulation data, analysed using a Markov state model. Seven metastable conformations with different binding pocket structures are found that interconvert at timescales of tens of microseconds. These conformations differ in their substrate-binding affinities and binding/dissociation rates. For each metastable state, corresponding solved structures of Trypsin mutants or similar serine proteases are contained

SUBMITTER: Plattner N 

PROVIDER: S-EPMC4506540 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature