NIH R01 · 2025
"On the Fly" Time Resolved Cryo-EM Studies of Intermediate HIV-1 RT Transition States
SUMMARY Historically, interactions between substrates and/or inhibitors and enzymes have been viewed in terms of binding of small molecules to relatively rigid protein targets. However, computational and experimental studies have revealed that many proteins, in particular DNA polymerases, undergo molecular motions over a wide range of timescales. Such conformational flexibility is critical for enzymatic activity, drug action and drug resistance. Moreover, contemporary structural biology approaches, such as X-ray crystallography, only have the ability to resolve the structures of thermodynamically stable species, and cannot inform on kinetic intermediates. Our group has developed…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.