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

技术概述：这个材料世界网络合作项目的目标是将蛋白质的分子结构与其相互作用能和相行为联系起来，该项目涉及英国布兰迪斯大学、特拉华大学和剑桥大学的教师。研究小组将对纯化蛋白质进行综合实验，并基于现实模型表示进行模拟，以便进行直接比较。他们将构建两类蛋白质分子模型，一类基于原子结构信息，用于与实验进行定量比较，另一类基于这些信息，但提供最小模型，以阐明蛋白质溶液的平衡相图和相分离动力学的一般性质。将模拟能量和自由能景观，相互比较，并与相行为和渗透二次维里系数的测量结果进行比较。成核速率的测量和模拟将在经典成核模型的背景下进行解释，而单个临界核生长的测量和模拟将检验该模型的假设。动力学捕获状态，如非平衡凝胶和沉淀，将通过实验和模拟进行研究。将在模拟和实验中开发蛋白质溶液的时间处理协议，以便在干涉液体和晶体相之间的捕获状态中导航。非技术总结：在生物学中，由于生物环境的复杂性，哪些分子特性导致某些蛋白质结合以及哪些分子特性阻止相同的蛋白质在集中的细胞内环境中聚集的问题在很大程度上仍然没有答案。从生物材料自组装的角度来看，蛋白质-蛋白质相互作用与相行为之间的关系是基本的。如果材料界要为应用设计蛋白质，这个问题必须直接面对。这个合作材料世界网络项目的目标是将蛋白质的分子结构与其相互作用能量和相行为联系起来。更广泛的影响将是提高结构生物学中蛋白质结晶的成功率，控制药物应用中的蛋白质聚集，以及为药物输送应用开发新的蛋白质凝聚相，这些问题具有重大的科学和工业重要性。本项目由生物材料项目和材料研究部特别项目办公室支持。

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.