Atomic-level protein structure refinement using fragment-guided molecular dynamics conformation sampling.

ABSTRACT: One of critical difficulties of molecular dynamics (MD) simulations in protein structure refinement is that the physics-based energy landscape lacks a middle-range funnel to guide nonnative conformations toward near-native states. We propose to use the target model as a probe to identify fragmental analogs from PDB. The distance maps are then used to reshape the MD energy funnel. The protocol was tested on 181 benchmarking and 26 CASP targets. It was found that structure models of correct folds with TM-score >0.5 can be often pulled closer to native with higher GDT-HA score, but improvement for the models of incorrect folds (TM-score <0.5) are much less pronounced. These data indicate that template-based fragmental distance maps essentially reshaped the MD energy landscape from golf-course

SUBMITTER: Zhang J 

PROVIDER: S-EPMC3240822 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature