Structure and Dynamics of Viral Substrate Recognition and Drug Resistance: A Dissertation

摘要: Drug resistance is a major problem in quickly evolving diseases, including the human immunodeficiency (HIV) and hepatitis C viral (HCV) infections. The proteases (HIV protease HCV NS3/4A protease) are primary drug targets. At molecular level, reflects subtle change balance of recognition; resistant variants no longer effectively inhibited by competitive molecules but can process natural substrates with enough efficiency for survival. Therefore, inhibitors that better mimic substrate binding features should result more robust flat profiles. native adopt consensus volume when bound to enzyme, envelope. most severe mutations occur at residues contacted outside To guide design inhibitors, we investigate shared varied properties protein dynamics taken into account define dynamic envelope both proteases. compared detect structural basis mutation patterns. Comparative analyses solid list not inhibitors. This study help guiding development novel paying attention differences between versus