Title

Functional group based Ligand binding affinity scoring function at atomic environmental level

Authors

Pritish Kumar Varadwaj^1, * and Tapobrata Lahiri¹

Affiliation

¹Indian Institute of Information Technology, Allahabad, 211012, India

Email

pritish@iiita.ac.in; * Corresponding author

Article Type

Hypothesis

Date

received September 28, 2008; accepted December 06, 2008; published January 12, 2009

Abstract

Use of knowledge based scoring function (KBSF) for virtual screening and molecular docking has become an established method for drug discovery. Lack of a precise and reliable free energy function that describes several interactions including water-mediated atomic interaction between amino-acid residues and ligand makes distance based statistical measure as the only alternative. Till now all the distance based scoring functions in KBSF arena use atom singularity concept, which neglects the environmental effect of the atom under consideration. We have developed a novel knowledge-based statistical energy function for protein-ligand complexes which takes atomic environment in to account hence functional group as a singular entity. The proposed knowledge based scoring function is fast, simple to construct, easy to use and moreover it tackle the existing problem of handling molecular orientation in active site pocket. We have designed and used Functional group based Ligand retrieval (FBLR) system which can identify and detect the orientation of functional groups in ligand. This decoy searching was used to build the above KBSF to quantify the activity and affinity of high resolution protein-ligand complexes. We have proposed the probable use of these decoys in molecular build-up as a de-novo drug designing approach. We have also discussed the possible use of the said KSBF in pharmacophore fragment detection and pseudo center based fragment alignment procedure.

Keywords

ontology; small molecule; functional group; pharmacophore; semantic similarity; scoring function; knowledgebase; Distance based scoring

Citation

Varadwaj & Lahiri, Bioinformation 3(6): 268-274 (2009)

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.