Molecular Dynamics Characterization of Protein Crystal Contacts in Aqueous Solutions

Abstract

We employ nonequilibrium molecular dynamics simulation to characterize the effective interactions between lysozyme molecules involved in the formation of two hydrophobic crystal contacts. We show that the effective interactions between crystal contacts do not exceed a few kT, the range of the attractive part of the potential is less than 4 angstroms, and, within this range, there is a significant depletion of water density between two protein contacts. Our findings highlight the different natures of protein crystallization and protein recognition processes.

Characterizing protein crystal contacts and their role in crystallization: rubredoxin as a case study

“…In particular, although anisotropy plays a key role in physical models for protein crystallization 39–41 , little characterization of the directional interaction between proteins at crystal contacts has been done 42 , leaving most of the physical assumptions behind patchy models untested. Can these models explain the results of crystallographic experiments if they are parameterized using actual protein-protein interactions?…”

Crystallization of asymmetric patchy models for globular proteins in solution

“…The introduction of bond directionality in symmetric "patchy" models is aimed at better representing the effective protein-protein interactions that drive their crystallization [18,19]. Yet the most commonly studied versions of these models have symmetric and interchangeable patches, which are atypical of real proteins [4,[20][21][22] and insufficient to describe the assembly of even the simplest of globular proteins [22,23]. In this article, we investigate the role of patch geometry and bond energy asymmetry on the phase diagram and assembly dynamics * Corresponding author: patrick.charbonneau@duke.edu of a coarse-grained protein model of rigid globular proteins in aqueous solution.…”

“…By symmetry, an analogous definition holds for θ 2,2i−1 . Here, the short radial extent of the square-well attraction, λ i = 1.1σ [37], and its surface coverage measured by the semiopening angle of its conical segment, δ i = cos −1 (0.89), are chosen to be typical of protein-protein interactions [20,23]. In contrast, the patch position on the surface and the bond energy i are randomly chosen, under the sole constraint that the lattice formed by simply bonding the patches is the orthorhombic P 2 1 2 1 2 1 .…”

Soft matter perspective on protein crystal assembly

“…Existing chemical databases do not suffice, however, to generalize this approach with much accuracy. More recent attempts have used all-atom molecular dynamics simulations of protein pairs in solutions in order to extract the angularly-resolved potential of mean force [125,145,146]. Within the quality of the selected molecular force fields, these simulations offer a reasonable characterization of known crystal contacts.…”