Accelerating drug discovery through tight integration of expert molecular design and predictive scoring.
Modeling protein-ligand interactions has been a central goal of computational chemistry for many years. We here review recent progress toward this goal, and highlight the role free energy calculation methods and computational solvent analysis techniques are now having in drug discovery. We further describe recent use of these methodologies to advance two separate drug discovery programs targeting acetyl-CoA carboxylase and tyrosine kinase 2. These examples suggest that tight integration of sophisticated chemistry teams with state-of-the-art computational methods can dramatically improve the efficiency of small molecule drug discovery.
Schrodinger Inc., New York, NY 10036, United States.
Robert
R
Abel
Schrodinger Inc., New York, NY 10036, United States.
Sayan
S
Mondal
Nimbus Therapeutics, Cambridge, MA 02141, United States.
Craig
C
Masse
Schrodinger Inc., New York, NY 10036, United States.
Jeremy
J
Greenwood
Nimbus Therapeutics, Cambridge, MA 02141, United States.
Geraldine
G
Harriman
Nimbus Therapeutics, Cambridge, MA 02141, United States.
Mark A
MA
Ashwell
Schrodinger Inc., New York, NY 10036, United States.
Sathesh
S
Bhat
Nimbus Therapeutics, Cambridge, MA 02141, United States.
Ronald
R
Wester
Schrodinger Inc., New York, NY 10036, United States.
Leah
L
Frye
Nimbus Therapeutics, Cambridge, MA 02141, United States.
Rosana
R
Kapeller
Department of Chemistry, Columbia University, New York, NY 10027, United States. Electronic address: raf8@columbia.edu.
Richard A
RA
Friesner
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D053634:TYK2 Kinase; D000103:Acetyl-CoA Carboxylase