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Beyond Bioinformatics | |
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Title
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Molecular docking studies on DMDP derivatives as human DHFR inhibitors | |||||||||||||||||||||||||||
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Authors
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Vivek Srivastava1, Ashutosh Kumar2, Bhartendu Nath Mishra1, * and Mohammad Imran Siddiqi2
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Affiliation
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1Department of Biotechnology, Institute of Engineering and Technology Sitapur Road, Lucknow-21; 2Molecular and Structural Biology Division, CDRI, Lucknow-01
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profbnmishra@gmail.com; * Corresponding author
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Article Type
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Hypothesis | ||||||||||||||||||||||||||||
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Date
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received June 18, 2008; accepted October 30, 2008; published December 06, 2008 | ||||||||||||||||||||||||||||
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Abstract |
Molecular docking is routinely used for understanding drug–receptor interaction in modern drug design. Here, we describe the docking of 2, 4-diamino-5-methyl-5-deazapteridine (DMDP) derivatives as inhibitors to human dihydrofolate reductase (DHFR). We docked 78 DMDP derivates collected from literature to DHFR and studied their specific interactions with DHFR. A new shape-based method, LigandFit, was used for docking DMDP derivatives into DHFR active sites. The result indicates that the molecular docking approach is reliable and produces a good correlation coefficient (r2 = 0.499) for the 73 compounds between docking score and IC50 values (Inhibitory Activity). The chloro substituted naphthyl ring of compound 63 makes significant hydrophobic contact with Leu 22, Phe 31 and Pro 61 of the DHFR active site leading to enhanced inhibition of the enzyme. The docked complexes provide better insights to design more potent DHFR inhibitors prior to their synthesis.
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Keywords |
DHFR inhibitors; DMDP derivatives; molecular docking; drug; receptor
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Citation |
Srivastava et al., Bioinformation 3(4): 180-188 (2008) | ||||||||||||||||||||||||||||
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Edited by |
P. Kangueane | ||||||||||||||||||||||||||||
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ISSN |
0973-2063 | ||||||||||||||||||||||||||||
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Publisher |
Biomedical Informatics Publishing Group | ||||||||||||||||||||||||||||
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Copyright |
Publisher | ||||||||||||||||||||||||||||
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Copyright Transfer Agreement
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The authors of published articles in Bioinformation automatically transfer the copyright to the publisher upon formal acceptance. However, the authors reserve right to use the information contained in the article for non commercial purposes.
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License
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This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
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