Protein-ligand interactions / Protein-ligand docking / Pharmacophore modeling / Template-based docking / Scaffold replacement / R-group exploration / Bioisosteric transformations / Ligand properties / PLIFs
This workshop presents common molecular modeling and design techniques for identifying, optimizing, and prioritizing small-molecule drug candidates. The workshop begins by describing structure preparation and pocket analysis to understand key protein-ligand interactions. Participants will explore template-based docking of congeneric series and pharmacophore-guide docking (to preserve key interactions) to predict how small molecules bind to a protein target. This workshop also presents a series of de novo fragment-based drug design applications, focusing on scaffold hopping and fragment growing methods to generate novel compound ideas, optimize structures in the pocket, and score them. It also discusses the use of molecular descriptors, protein-ligand interaction fingerprints (PLIFs), and pharmacophore models to guide the drug design process. Finally, a method for generating closely related analogs through bioisosteric replacements is presented.