Experimental accuracy in protein structure refinement via molecular dynamics simulations.

ABSTRACT: Refinement is the last step in protein structure prediction pipelines to convert approximate homology models to experimental accuracy. Protocols based on molecular dynamics (MD) simulations have shown promise, but current methods are limited to moderate levels of consistent refinement. To explore the energy landscape between homology models and native structures and analyze the challenges of MD-based refinement, eight test cases were studied via extensive simulations followed by Markov state modeling. In all cases, native states were found very close to the experimental structures and at the lowest free energies, but refinement was hindered by a rough energy landscape. Transitions from the homology model to the native states require the crossing of significant kinetic barriers on at least

SUBMITTER: Heo L 

PROVIDER: S-EPMC6310835 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature