Switching Gō-Martinifor Investigating Protein Conformational Transitions and Associated Protein-Lipid Interactions

Abstract

AbstractProteins are dynamic biomolecules that can transform between different conformational states when exerting physiological functions, which is difficult to simulate by using all-atom methods. Coarse-grained Gō-like models are widely-used to investigate large-scale conformational transitions, which usually adopt implicit solvent models and therefore cannot explicitly capture the interaction between proteins and surrounding molecules, such as water and lipid molecules. Here, we present a new method, namedSwitching Gō-Martini, to simulate large-scale protein conformational transitions between different states, based on the switching Gō method and the coarse-grained Martini 3 force field. The method is straight-forward and efficient, as demonstrated by the benchmarking applications for multiple protein systems, including glutamine binding protein (GlnBP), adenylate kinase (AdK), andβ2-adrenergic receptor (β2AR). Moreover, by employing theSwitching Gō-Martinimethod, we can not only unveil the conformational transition from the E2Pi-PL state to E1 state of the Type 4 P-type ATPase (P4-ATPase) flippase ATP8A1-CDC50, but also provide insights into the intricate details of lipid transport.