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Virtual Screening: C371 Fall 2004
Virtual Screening: C371 Fall 2004
C371
Fall 2004
INTRODUCTION
• Virtual screening – Computational or in silico
analog of biological screening
– Score, rank, and/or filter a set of structures using one
or more computational procedures
– Helps decide:
• Which compounds to screen
• Which libraries to synthesize
• Which compounds to purchase from an external source
– Also used to analyze the results of HTS screening
runs
Ways to Assess Structures from a
Virtual Screening Experiment
• Use a previously derived mathematical model
that predicts the biological activity of each
structure
• Run substructure queries to eliminate molecules
with undesirable functionality
• Use a docking program to ID structures
predicted to bind strongly to the active site of a
protein (if target structure is known)
• Filters remove structures not wanted in a
succession of screening methods
Main Classes of Virtual Screening
Methods
• Depend on the amount of structural and
bioactivity data available
– One active molecule known: perform similarity search
(ligand-based virtual screening)
– Several active molecules known: try to ID a common
3D pharmacophore, then do a 3D database search
– Reasonable number of active and inactive structures
known: train a machine learning technique
– 3D structure of the protein known: use protein-ligand
docking
Virtual Screening Methods for Non-
Specific Targets