High Energy Channeling and Malleable Transition States: Molecular Dynamics Simulations and Free Energy Landscapes for the Thermal Unfolding of Protein U1A and 13 Mutants.

ABSTRACT: The spliceosome protein U1A is a prototype case of the RNA recognition motif (RRM) ubiquitous in biological systems. The in vitro kinetics of the chemical denaturation of U1A indicate that the unfolding of U1A is a two-state process but takes place via high energy channeling and a malleable transition state, an interesting variation of typical two-state behavior. Molecular dynamics (MD) simulations have been applied extensively to the study of two-state unfolding and folding of proteins and provide an opportunity to obtain a theoretical account of the experimental results and a molecular model for the transition state ensemble. We describe herein all-atom MD studies including explicit solvent of up to 100 ns on the thermal unfolding (UF) of U1A and 13 mutants. Multiple MD UF trajectories a

SUBMITTER: Dang NL 

PROVIDER: S-EPMC9312810 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature