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

TL;DR

This study combines computational simulations and modeling to understand protein crystal contacts, specifically in rubredoxin, bridging structural biology and soft matter perspectives to improve crystallization strategies.

Contribution

It introduces a hybrid approach using atomistic simulations and patchy particle models to analyze protein contacts and compare with experimental data.

Findings

Identified key features of protein-protein interactions for crystallization

Validated patchy particle models against experimental phase diagrams

Provided insights to enhance protein crystallization methods

Abstract

The fields of structural biology and soft matter have independently sought out fundamental principles to rationalize protein crystallization. Yet the conceptual differences and the limited overlap between the two disciplines have thus far prevented a comprehensive understanding of the phenomenon to emerge. We conduct a computational study of proteins from the rubredoxin family that bridges the two fields. Using atomistic simulations, we characterize their crystal contacts, and accordingly parameterize patchy particle models. Comparing the phase diagrams of these schematic models with experimental results enables us to critically examine the assumptions behind the two approaches. The study also reveals features of protein-protein interactions that can be leveraged to crystallize proteins more generally.