Free Energies in Biomolecular Systems: Development and Applications of Theoretical and Computational Approaches

University Of Chicago, Chicago IL

Investigators

Abstract

Biology, at the atomic level, is fundamentally controlled by the activity and interactions of a wide range of different molecules. Some, such as proteins and nucleic acids, are large and highly complex chemical structures called macromolecules. Others are small chemical compounds, which can be as simple as a single water molecule. One of the most basic questions about any of the molecules in the living cell is the manner by which they interact and associate with one another. How molecules recognize and bind to a specific partner plays a key role in biology. For example, this is one of the ways biological "signals" and information are transmitted and communicated within and between living cells, and how specific processes are triggered and synchronized. The research project consists in improving the theoretical and computational methods to calculate and predict accurately how molecules bind to one another. According to the theory of statistical thermodynamics, the quantity that controls the association of molecules is the "binding free energy". This mathematically well-defined quantity can be calculated using computer simulations of atomic models of the molecules of interest. One method, which is called "molecular dynamics" simulation, can help elucidate the fundamental principles governing the binding of biological molecules at the atomic level. Efforts in this area have great intellectual merit because biology is entering a quantitative era that requires an ability to predict the binding of molecules. This research is carried out in an academic environment and one essential aspect to the broader impact is the education and training of highly qualified personnel. The students and postdoctoral researchers involved in the research project will ultimately join the job market, either in academia or in industry, and their advanced skills will contribute to the vitality of society. Furthermore, improving the ability to predict binding accurately using computations has great pragmatic value and is expected to have a broad impact on a vast array of fundamental problems in biology and chemistry. For example, technological advances in this area could be used to engineer and design better method to detect, capture, and extract toxic molecules from the environment (bioremediation). Lastly, all the new knowledge produced by the research in the form of theories, explanation, and computer programs is freely disseminated via the PI's lab web site for the benefit of the entire community.