Coarse-Grained and Atomistic Modeling of Anisotropic Atomic Fluctuations in Protein Crystal Structures

Abstract

Protein atomic fluctuations can be probed by x-ray crystallography in the form of Anisotropic Displacement Parameters (ADP). In this study, we assess the accuracy of different coarse-grained and atomistic models that include protein-environment interactions in a protein crystal in comparison with experimental ADPs. We use a coarse-grained Elastic Network Model (ENM) with three different boundary conditions (see figure) to model protein-environment interactions, and an atomistic model using a CHARMM force-field. For a large list of high-resolution protein crystal structures, we find that optimal ADP modeling is achieved by weak protein-environment interactions as compared to internal interactions within a protein structure. Therefore, the internal dynamics of a protein is only weakly perturbed by crystal packing. We also find no improvement in the accuracy of ADP modeling by using the atomistic model over the coarse-grained ENM.View Large Image | View Hi-Res Image | Download PowerPoint SlideFigure. A protein-environment system constructed from a protein crystal of oxy-myoglobin (PDB code: 1a6m) with the main protein in red, the nearest neighbors in green, and the next nearest neighbors in blue. The main protein and the nearest neighbors are unconstrained while the next nearest neighbors are fixed.