Molecular field technology applied to virtual screening and finding the bioactive conformation

Abstract

Virtual screening is being applied to reduce the high-throughput screening bottleneck in many pharmaceutical companies and to reduce compound wastage. Cresset’s ligand-based virtual screening technology using molecular fields can facilitate rapid identification of novel chemotypes from biologically testing only 200 – 1000 compounds. Four molecular fields calculated using the interaction of different probe atoms with the ligand are sufficient to describe how a ligand binds to its protein. Compounds with similar fields to known active ligands are predicted to have a high probability of showing similar activity. As binding is related to field similarity, this property has been exploited further to predict the bioactive conformation of small sets of structurally diverse active ligands starting from the two-dimensional structures alone without knowledge of the target site structure.

Keywords::

• bioactive conformation
• CCK2
• Cdk2
• molecular interaction field
• molecular similarity
• pharmacophore
• scytalone dehydratase
• virtual screening

Acknowledgements

The authors would like to thank C Low and B Kalindjian of the James Black Foundation for their scientific input.

Notes