Domain Motions in the Interpretation of Neutron Spin Echo Spectroscopy and Molecular Dynamic Simulation: A Case Study of Phosphoglycerate Kinase

Abstract

The conformational dynamics of proteins are important for functions. Large-scale domain motions of enzymes are often essential for their biological function. Few techniques are available that can directly probe protein motions. Among the most direct is molecular dynamics simulation in which, using an empirical potential energy function, the equations of motion of a system of atoms are solved numerically. In this way detailed description of protein dynamics can be built up for timescales up to about 100 ns. Integration of molecular dynamics simulations and neutron scattering provide insights of process in the proteins in the atomic details. An exciting new development in the experimental detection of functionally-important domain motions in proteins is the application of neutron spin-echo spectroscopy (NSE). Spin echo directly probes coherent (i.e., pair correlated) scattering on the 10-100 ns timescale. Recent work has demonstrated that domain motions in the two domain protein phosphoglycerate kinase (PGK) can be positively identified and characterized with this technique. Inspired by these results, we performed molecular dynamics simulation of PGK. The measurable quantities, the intermediate scattering functions and small-angle neutron scattering profile were directly calculated from the MD trajectories. All results are in very good agreement with experimental data. Principal component analysis (PCA) was used to characterize the molecular dynamics trajectory. PCA extracts the essential motions sampled by MD simulation: the principal component modes. We have shown that combination of neutron scattering and molecular dynamics simulation is a powerful tool for characterization large scale motions in proteins.