A detailed understanding of the physicochemical factors that control protein-ligand binding affinities is of fundamental importance in order to address many questions in biochemistry and pharmacology. The biotin-streptavidin complex serves as an excellent model system for a high-affinity protein-ligand complex that is amenable to both detailed biophysical measurements and computational studies. Previous x-ray crystallography and micro-calorimetry experiments in our laboratory have yielded some surprising results, namely several distal point mutations (I.e., point mutations far from the ligand binding site) that have no impact on equilibrium structure but that reduce biotin binding affinity dramatically. Molecular dynamics simulations, coupled with quantum mechanics/molecular mechanics calculations, have proven essential to help explain the basis for these unexpected experimental observations. Recent experimental measurements for other protein-ligand complexes suggest that our streptavidin system results are relevant for many systems.

Computational studies help explain unexpected experimental results in the biotin-streptavidin complex and reveal important concepts for general protein-ligand interactions

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.