Unveiling Functional Protein Motions with Picosecond X-ray Crystallography and Molecular Dynamics Simulations

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Oct 19

PMID 15489270

Citations 36

Authors

Gerhard Hummer

Friedrich Schotte

Philip A Anfinrud

Affiliations

Soon will be listed here.

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 cavities, with passage between them involving correlated protein-ligand motions. The simulations also suggest how picosecond protein motions modulate the functional dissociation of oxygen and suppress the geminate recombination of toxic carbon monoxide.

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