Title

Authors

Affiliation

¹Department of Bioinformatics, Alagappa University, Karaikudi 630 004, India; ²Musculoskeletal Disease Center, JLP VA Medical Center, Loma Linda, USA; ³Dept of Medicine, Loma Linda University, Loma Linda, USA.

Email

mkbioinformatics@gmail.com; *Corresponding author

Article Type

Hypothesis

Date

Received July 17, 2012; Accepted July 23, 2012; Published August 03, 2012

Small structured chemical molecules are importance in the field of molecular medicine since their pharmacokinetic and pharmacodynamic properties are predictable and because of its ability to bind with target molecules and execute biological function. In this study, we engaged computer-aided methodology in combination with molecular docking and pharmacophore filtering to identify chemical compounds that can increase the synthesis of vitamin D receptor (VDR) since its lower expression leads to calcium phosphate metabolic disorders in Chronic Kidney Disease. Energy-optimized pharmacophore was mapped using available agonists for VDR. Based on the e-pharmacophore, we propose the pharmacophore features that should present in VDR agonists. The resulting pharmacophore model contains one hydrogen bond acceptor (A), one hydrogen bond donor (D) and two hydrophobic regions (H). Using these features pharmacophore had been made and screened against large public library of compounds (Asinex, TOSLab, Bindin g and Zinc database) to find potential lead compounds. The compounds which yield fitness score of more than 1.0 were further subjected to Glide HTVS, SP and XP. Glide docking results revealed five hits (BD_230, BD_12938, BD_18601, BD_19517 and BD_19584) were identified as potential lead molecules against calcium phosphate metabolic disorders.

Keywords

Chronic Kidney Disease, VDR agonists, E-Pharmacophore mapping and Molecular docking

Citation

Nagamani et al. Bioinformation 8(15): 705-710 (2012)
 

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.