Exploring GB1 Dimerization Pathway Markov State Models

Abstract

Markov state model (MSM) is a suitable method of studying the intermediate states and pathways during the binding/dimerization process of proteins. The dimerization structure of GB1 can have two distinct shapes; domain swapped (DS) and side-by-side (SS) where the former is more stable as conformed by both simulation1 and experiment2 . Here we employ a 20 microsecond long molecular dynamics trajectory1 of GB1 dimerization starting from monomer states to construct a MSM. To identify the slow coordinates for investigation of dimerization process, time-based independent component analysis (TICA) was performed on internal coordinates such as center of geometry distance, root mean square deviation and inverse distance between contact monomers. A density based clustering algorithm combined with a dynamical coring and clustering strategy was used to identify the metastable states. The transition between the states obtained from the Markov model shows pathways from monomer states to dimer states which can be direct without any intermediate state or indirect having different intermediate states.