Alan Fersht: From covalent transition states in chemistry to noncovalent in biology

Lecture by Professor Alan Fersht, University of Cambridge, at the Molecular Frontiers Symposium "Frontiers of New Knowledge in Science" in Hong Kong, Nov 15-17, 2024.

Abstract
From covalent transition states in chemistry to noncovalent in biology:
from Brønsted b- to Φ-value analysis

Solving the mechanism of a chemical reaction requires determining the structures of all the ground states on the pathway and the elusive transition states linking them. 2024 is the centenary of Brønsted’s landmark paper that introduced the β-value and structure-activity studies as the only experimental means to infer the structures of transition states. It involves making systematic small changes in the covalent structure of the reactants and analysing changes in activation and equilibrium free energies. Protein engineering was introduced 60 years later for an analogous procedure, Φ 汀 value analysis, to analyse the noncovalent interactions in proteins central to biological chemistry: from the use of binding energy in enzymatic catalysis; specificity; and the pathway of protein folding. I give a personal account on how a background in organic and physical chemistry in particular has guided me throughout working at the interface of chemistry, biology and physics for problem solving and discovery