Unveiling functional protein motions with picosecond x-ray crystallography and molecular dynamics simulations.

ABSTRACT: A joint analysis of all-atom molecular dynamics (MD) calculations and picosecond time-resolved x-ray structures was performed to gain single-molecule insights into mechanisms of protein function. Ensemble-averaged MD simulations of the L29F mutant of myoglobin after ligand dissociation reproduce the direction, amplitude, and time scales of crystallographically determined structural changes. This close agreement with experiments at comparable resolution in space and time validates the individual MD trajectories. From 1,700 single-molecule trajectories, we identified and structurally characterized a conformational switch that directs dissociated ligands to one of two nearby protein cavities. Subsequent ligand migration proceeds through a network of transiently interconnected internal cavitie

SUBMITTER: Hummer G 

PROVIDER: S-EPMC523450 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature