Characterization of sub-nanosecond dynamics of the molten globule state of α-lactalbumin using quasielastic neutron scattering and molecular dynamics simulations

Abstract

The dynamics of α-lactalbumin in the native and molten globule states in solution was investigated using quasielastic neutron scattering and molecular dynamics simulations. We generated 2 nanosecond molecular dynamics trajectories at 300 K of α-lactalbumin solvated in a water box in the native state, and a putative member of the ensemble of conformations of the molten globule state generated by simulation at high temperature. Overall the agreement between the measured and calculated dynamical structure factors is good. Preliminary analysis of the simulated dynamics of the molten globule state revealed a strong heterogeneity of motions along the protein backbone, with larger amplitudes in the regions of the protein that unfold, mainly the β-sheet region. The results presented here demonstrate the utility of using a combination of neutron scattering measurements and molecular dynamics simulations to characterize and quantify, in a sequence-specific fashion, the differences in dynamics between the native and partially folded states of proteins on the time scale (∼100 ps) and length scale (a few to tens of A) probed by current neutron spectrometers.