Title

Docking of phosphonate and trehalose analog inhibitors into M. tuberculosis mycolyltransferase Ag85C: Comparison of the two scoring fitness functions GoldScore and ChemScore, in the GOLD software

Authors

Manoj Kumar Annamala, Krishna Kishore Inampudi, Lalitha Guruprasad*

Affiliation

School of Chemistry,University of Hyderabad, Hyderabad 500 046, India

Email

lgpsc@uohyd.ernet.in

Phone

+91 040 2313 4820

Fax

+91 040 2310 4260; * Corresponding author

Article Type

Hypothesis

Date

received July 27, 2006; revised December 13, 2006; accepted December 24, 2006; published online January 02, 2007

Abstract

The Ag85 family enzymes are responsible for the synthesis of cell wall components in mycobacterial species. Inhibitors to these enzymes are potential antimycobacterial agents. We have carried out the docking of phoshonate and trehalose analog inhibitors into the three dimensional structure of mycolyltransferase enzyme, Ag85C of M. tuberculosis using the GOLD software. The inhibitor binding positions and affinity were evaluated using both the scoring fitness functions- GoldScore and ChemScore. We observed that the inhibitor binding position identified using the GoldScore was marginally better than the ChemScore. A qualitative agreement between the reported experimental biological activities (IC50) and the GoldScore was observed. We identified that amino acid residues Arg541, Trp762 are important for inhibitor recognition via hydrogen bonding interactions. This information can be exploited to design Ag85C specific inhibitors.  

Keywords

M. tuberculosis; drug design; docking; mycolyltransferases; trehalose analogs; phosphonate inhibitors

Citation

Edited by

N. Srinivasan

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.