CGSO invited speaker
About the Seminar:
The thermodynamics of molecular recognition by proteins is a central determinant of complex biochemistry. For over a half-century, detailed cryogenic structures have provided deep insight into the energetic contributions to ligand binding by proteins. We have been pursuing the elusive contributions of conformational entropy. The development of a dynamical proxy based on solution NMR-relaxation methods has revealed an unexpected richness in the contributions of conformational entropy to the thermodynamics of ligand binding. The evolution of the so-called “entropy meter” from its model-dependent roots to its current empirically calibrated form will be presented. From this work, it is now abundantly clear that conformational entropy is often a critical element of molecular recognition by soluble proteins. The role of solvent entropy has also been examined using a novel NMR approach based on the favorable attributes of confinement provided by reverse micelle encapsulation. Recently, we have approached integral membrane proteins, which have eluded a similar characterization. The first examples, pSRII and Omp W, are found to be more dynamic in the ps-ns time regime than any previously characterized protein. The corresponding conformational entropy apparently stabilizes the folded state in the absence of the classic hydrophobic effect. Finally, despite these insights, there remains a discomforting disconnect between protein structure and conformational entropy. Prompted by the dynamical response of barnase to high pressure, we performed an analysis of the small packing imperfections or voids surrounding over 2,500 methyl-bearing side chains having determined order parameters. Changes in unoccupied volume as small as a water molecule surrounding buried side chains greatly affects fast motion. The discovered relationship begins to permit construction of a united view of the relationship between changes in the internal energy, provided by structural analysis, and the conformational entropy, as represented by fast internal motion, in the thermodynamics of protein function.
About the Speaker:
Professor Josh Wand is Professor and Head of Biochemistry and Biophysics at Texas A&M University. He also holds joint appointments in the Departments of Chemistry and Molecular and Cellular Medicine. Dr. Wand received his Ph.D. in biophysics from the University of Pennsylvania in 1984. Following postdoctoral training at the National Research Council of Canada in solid-state NMR, he joined the faculty of the Institute for Cancer Research. He subsequently spent time on the faculties of the University of Illinois at Urbana-Champaign and the State University of New York at Buffalo. He was the Benjamin Rush Professor of Biochemistry & Biophysics at the University of Pennsylvania for two decades before joining Texas A & M University in 2019. Dr. Wand teaches undergraduate biochemistry and graduate topics in biophysics and chemistry. He has received over 25 M in research grant support over his career and published over 200 research and review articles and given over 200 invited seminars and presentations at Universities and conferences throughout the world. He is a Fellow of the Biophysical Society and a Fellow of the American Physical Society. He continues to apply advanced solution NMR and other techniques to questions in protein biophysics with emphasis on dynamics, entropy and hydration in protein functions such as allostery and a novel route to drug discovery.
