Advanced Small Molecule Docking
Advanced docking workflows encountered in drug discovery projects are described, which include a range of related topics from the application of pharmacophore constraints in docking to the analysis of protein-ligand interaction fingerprints (PLIF) generated from docked poses. Examples include: (1) general docking with applied pharmacophore constraints, (2) template-based docking using a scaffold or fragment to guide placement, and (3) covalent docking to generate, rank and score ligands that are covalently bound to a protein/receptor. Leveraging multiple processing capacity is also presented.
02:24 Quick prep protocol for receptor structure setup
03:50 Fundamentals of large-scale docking workflows
04:47 Speed improvements in MOE 2020—confirmation placement and parallelization
06:14 Protein annotation and guided docking for targeted screening
08:30 Scenario-based docking panel overview & options
11:18 Creating pharmacophore features from co-crystal ligands
14:08 Incorporating excluded volume to speed screening
16:30 Using ligand databases with pre-generated confirmations
17:56 Screening for CDK2 inhibitors in 90 seconds & enrichment analysis
20:44 Leveraging cluster and cloud computing for vast libraries
25:02 Validation of docking results and enrichment factors
28:55 Working with APO receptor structures using receptor annotations
33:29 Template-based docking for scaffold-specific screening
39:56 Covalent docking: preparing reactive ligands & handling stereochemistry
45:17 Incorporating pharmacophores into other docking scenarios
