Collaborative Research: Materials World Network: Protein Phase Behavior - Experiments and Simulations.

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TECHNICAL SUMMARY:The goal of this collaborative Materials World Network project involving faculty at Brandeis University, the University of Delaware, and the University of Cambridge in the United Kingdom is to relate the molecular structure of proteins to their interaction energies and phase behavior. The research teams will undertake an integrated program of experiment on purified proteins and simulations based on realistic model representations that will allow direct comparisons. They will construct two classes of molecular models of proteins, one based on atomistic structural information for quantitative comparison with experiment and the other guided by such information but providing a minimal model to elucidate generic properties of the equilibrium phase diagrams and phase separation kinetics of protein solutions. The energy and free energy landscapes will be simulated, compared with each other and with measurements of phase behavior and of osmotic second virial coefficients. Measurements and simulations of nucleation rates will be interpreted in the context of the classical nucleation model, while measurements and simulations of the growth of individual precritical nuclei will test the assumptions of that model. Kinetically arrested states, such as non-equilibrium gels and precipitates, will be studied by experiment and simulation. Protocols for the temporal processing of protein solutions will be developed in simulations and experiment in order to navigate around the arrested states that intervene between the liquid and crystal phases.NON-TECHNICAL SUMMARY:In biology, the question of which molecular properties lead some proteins to associate and which prevent the same proteins from aggregating in the concentrated intracellular environment remains largely unanswered because of the complexity of the biological milieu. From the perspective of self-assembly of biomaterials, the relationship between protein-protein interactions and phase behavior is fundamental. If the materials community is going to engineer proteins for applications, this problem must be directly confronted. The goal of this collaborative Materials World Network project is to relate the molecular structure of proteins to their interaction energies and phase behavior. The broader impact will be to improve the success rate of protein crystallization for structural biology, to control protein aggregation for pharmaceutical applications and to develop novel condensed phases of proteins for applications of drug delivery, problems of significant scientific and industrial importance.This project is supported by the Biomaterials program and the Office of Special Programs, Division of Materials Research.