RUI: Understanding the Self-Assembly of Globular Proteins: Phase Behavior, Interactions, and Chirality

Yeshiva University, New York NY

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 0901260 PI: Asherie, Neer ORG: Yeshiva University Title: RUI: Understanding the Self-Assembly of Globular Proteins: Phase Behavior, Interactions, and Chirality INTELLECTUAL MERIT: Protein self-assembly is not well understood; it is not possible to predict what will happen to a homogeneous solution of a protein when the conditions are changed. The long-term goal of the proposal is to make it possible to predict the phase behavior of protein solutions and to learn to control protein self-assembly. There are three immediate objectives: (1) To determine the phase behavior of several globular proteins by light-scattering methods. The PI expects to provide comprehensive experimental evidence for the universal nature of protein phase behavior. (2) To construct realistic models for protein interactions. The PI will construct computationally tractable models with sufficient detail to capture the complexity of protein interactions. (3) To investigate new ways to control protein self-assembly. The PI will pursue our recent discovery that precipitant chirality can radically alter the crystallization of globular proteins. The governing hypothesis behind this work is that the phase behavior is controlled by a few parameters. One aim of the proposed work is to provide experimental evidence for this hypothesis. That is, there will be an attempt to determine the universal features of protein phase behavior. The experimental findings will be used to construct simple microscopic models for protein interactions that can describe the phase behavior. It will then become possible to predict the phase behavior of a protein from a few experimental measurements. The immediate impact of this work would be to greatly simplify studies involving proteins. Crystallizing proteins for structure determination would no longer depend so heavily on laborious trial and error, but instead would be based on a more precise approach that uses the phase diagram. This work will be done in the context of an RUI grant, involving undergraduate students in all aspects of a project that advances the frontiers of protein science. BROADER IMPACTS: The research on globular protein phase transitions detailed in this proposal will contribute towards long-term goals of establishing systematic means of producing protein crystals for structural studies, of constructing predictive theories of phase transitions in living cells and organisms, of providing for rational design of processes of importance in the biotechnology and food-processing industries, and of creating new and useful paradigms in statistical physics. The PI is among the first faculty to be hired at Yeshiva with a mandate to introduce a research component to the campus. His effectiveness in this role is demonstrated by two publications in the past year based on research done by undergraduates in his lab. He is developing new courses in Introductory Physics for Biology Students and Premedical Students, an intermediate level lecture/lab course in Waves and Optics for Science and Engineering majors, and an advanced Biophysics reading/lab course using the English tutorial approach. He is also faculty advisor to the Undergraduate Student Research Presentation forum, a biweekly meeting at which undergraduates present the results of their research projects. Finally, he is the organizer of a periodic lecture series for general audiences that seeks to explain the work behind the Nobel Prizes in Physics, Chemistry, Literature, Economics, Physiology, Medicine, and Peace.