Design rules for the self-assembly of a protein crystal

TL;DR

This paper investigates the self-assembly of open protein crystal structures, revealing that optimal assembly depends on specific thermodynamic conditions and nonspecific interactions, challenging traditional sphere-based theories.

Contribution

It introduces new design rules for protein crystal self-assembly, emphasizing the importance of thermodynamic driving force and interaction specificity, supported by theory and simulation.

Findings

Assembly not predicted by second virial coefficient

Optimal assembly requires thermodynamic driving force ~ thermal energy

Nonspecific interactions promote better assembly without phase separation

Abstract

Theories of protein crystallization based on spheres that form close-packed crystals predict optimal assembly within a `slot' of second virial coefficients and enhanced assembly near the metastable liquid-vapor critical point. However, most protein crystals are open structures stabilized by anisotropic interactions. Here, we use theory and simulation to show that assembly of one such structure is not predicted by the second virial coefficient or enhanced by the critical point. Instead, good assembly requires that the thermodynamic driving force be on the order of the thermal energy and that interactions be made as nonspecific as possible without promoting liquid-vapor phase separation.