bioRxiv Biochemistry
bioRxiv Biochemistry
5 years ago

Molecular determinants and bottlenecks in the unbinding dynamics of biotin-streptavidin

P., Tiwary
Biotin-streptavidin is a very popular system used to gain insight into protein-ligand interactions. It is well-known for its extremely long residence times, being one of the strongest known non-covalent interactions in nature, and is heavily used across the biotechnological industry. In this work we gain understanding into the molecular determinants and bottlenecks in the unbinding of the dimeric biotin-streptavidin system in its wild type and with N23A mutation. Using new enhanced sampling methods with full atomistic resolution, we reproduce experimentally reported residence times including their variation with the mutation. We also answer a longstanding question regarding cause/effect in the coupled events of bond stretching and bond hydration during unbinding and establish that in this system, it is the bond stretching which forms the bottleneck in the early parts of the unbinding. We believe these calculations represent a step forward in then use of atomistic simulations to study pharmacodynamics. An improved understanding of biotin-streptavidin unbinding dynamics should also have direct benefits in biotechnological and nanobiotechnological applications.

Publisher URL: http://biorxiv.org/cgi/content/short/176594v1

DOI: 10.1101/176594

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