MinActionPath2: path generation between different conformations of large macromolecular assemblies by action minimization

Abstract

Abstract Recent progress in solving macromolecular structures and assemblies by cryogenic electron microscopy techniques enables sampling of their conformations in different states that are relevant to their biological function. Knowing the transition path between these conformations would provide new avenues for drug discovery. While the experimental study of transition paths is intrinsically difficult, in-silico methods can be used to generate an initial guess for those paths. The Elastic Network Model (ENM), along with a coarse-grained representation (CG) of the structures are among the most popular models to explore such possible paths. Here we propose an update to our software platform MinActionPath that generates non-linear transition paths based on ENM and CG models, using action minimization to solve the equations of motion. The new website enables the study of large structures such as ribosomes or entire virus envelopes. It provides direct visualization of the trajectories along with quantitative analyses of their behaviors at http://dynstr.pasteur.fr/servers/minactionpath/minactionpath2_submission.