ABT-333 and ABT-072 are non-nucleoside NS5B polymerase inhibitors for hepatitis C, differing by a minor substituent change that impacts their drug development profiles. Here, the authors use advanced molecular simulations, including crystal structure prediction augmented with a new hydrate CSP algorithm and advanced MD simulations, to reveal how this change affects conformational preferences and interactions, highlighting the importance of physics-based modeling in drug design.
- Richard S. Hong
- Alessandra Mattei
- Ahmad Y. Sheikh
