Molecular dynamics approach observes rigid-body and liquid-like motion in protein crystals

X-ray crystallography is a mainstay method to study protein structure. However, its accuracy is limited, in part, by a lack of understanding about how crystalline proteins move. Scientists use a method known as diffuse scattering, which measures the cloudy features that lie between and beneath the sharp Bragg peaks in diffraction images, to study dynamics. Prior diffuse scattering studies, however, arrived at diverse conclusions about whether crystalline proteins are more liquid-like or rigid in their behavior.

Wych et al. used a new molecular dynamics approach to study crystalline protein dynamics. By focusing on the covariance of alpha-carbon position displacements in a 2x2x2 supercell of the staphylococcal nuclease protein, the group was able to observe liquid-like motions, and surprisingly rigid-body motions as well.

Their data showed that covariance decreases exponentially with distance between atoms, indicating liquid-like motions. In particular, inter-protein atom pairs, which dominated the overall statistics, showed liquid-like behavior.

Intra-protein atom pairs, in contrast, showed some rigid-body motions superimposed with liquid-like motions. The simulations’ diffuse scattering agreed substantially, if not perfectly, with the experimental data.

“Our paper explains some of the reason why different diffuse scattering studies might have come to different conclusions about what kinds of motions are present in protein crystals,” said author Michael Wall. “We can hope that this points in the right direction for getting more accurate crystal structures that have realistic descriptions of dynamics.”

Wall said that there are many opportunities for using molecular dynamics simulations to better understand crystalline protein dynamics. The group hopes that their findings in diffuse scattering help improve molecular dynamics force fields in general.

Source: “Liquid-like and rigid-body motions in molecular-dynamics simulations of a crystalline protein,” by David C. Wych, James S. Fraser, David L. Mobley, and Michael E. Wall, Structural Dynamics (2019). The article can be accessed at https://doi.org/10.1063/1.5132692 .