This document discusses virtual ligand screening (VLS) as an alternative to high-throughput screening for identifying potential drug candidates. It describes the VLS process, which involves selecting a target and compound library, preparing the target and ligands, running a docking simulation to analyze ligand-target binding, and prioritizing hits. The document outlines advantages of computational methods like VLS compared to experimental screening, as well as some limitations. It also provides examples of free and commercial docking engines that can be used and highlights challenges in VLS like accounting for receptor flexibility.
5. Why Computational Methods?
Accuracy as good as experimental (not
always!)
Can provide insights at molecular level
Fast
Easy to access
Can easily be automated
Economical
6. Computational Limitations
It only can simulate real conditions if
programmed
Larger systems are less accurate then
smaller systems
Need to be experimentally tested for
accuracy.
Does not look at the whole picture
8. The Detailed VLS Process
Select a Target
Select a Compound Library
Prepare Target
Prepare Ligand set
Select a Docking Engine
Analyze the Results
12. Ligand Preparation and VLS
Filters
Preparation
Assign charges
Generate possible Tautomers and
Stereoisomers (LigPrep)
Assign right protonation states
Filters
Physico-Chemical Filters (Lipinski Rule of
Five)
Similarity-based filters (take only diverse set
of compounds)
20. Challenges
Receptor Flexibility can
be tackled effectively by
exploiting Multiple diverse
Conformations of proteins
Multiple ways to
construct the ensemble:
Multiple crystal entries
Snapshots taken from MD
simulations
Figure: Hong and Tang, Biochemistry, Vol. 43, No. 16, 2004
22. Writing Manuscript/Report
Stand on the shoulders of giants
Take suggestions and ideas from experts
(poster presentation)
Check Consistency
Select an appropriate journal
“Copyright” does not mean “right to copy”
(Check plagiarized material)