Dr. Lazaridis’s research is in the area of Theoretical and Computational Biophysical Chemistry, which aims to understand how biological systems work in terms of the fundamental laws of Physics and Chemistry. Biomolecules, such as proteins and nucleic acids, have well defined conformations which often change in the course of their function. The goal of this research is to understand the forces that operate within and between biomolecules and develop quantitative mathematical models for their energy as a function of conformation. Such models are useful in many ways, such as predicting the three-dimensional structure from sequence, characterizing conformational changes involved in biological function, or predicting the binding affinity between two biomolecules.
One of the most difficult interactions to model is that between biomolecules and solvent. What is needed is a simple analytical function that gives the solvation free energy for an arbitrary conformation. Several years ago Dr. Lazaridis’s lab group developed a model (EEF1) based on the idea that solute atoms exclude solvent from the region they occupy. More recently the group extended this model to biological membranes, which are essentially a heterogeneous solvent. This will allow the study of the folding and stability of membrane proteins, a class of proteins of extraordinary importance whose structure and mechanism of action largely remain elusive to this date. It will also allow the study of the interaction of peptides and soluble proteins with membranes, which is implicated in many biological processes such as membrane fusion, innate immunity, or signal transduction.