Ligand‐based pharmacophore modelling and screening of DNA minor groove binders targeting Staphylococcus aureus |
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| Authors: | Periyasamy Vijayalakshmi Chandrabose Selvaraj Raja Mohmed Beema Shafreen Sanjeev Kumar Singh Shunmugiah Karutha Pandian Pitchai Daisy |
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| Affiliation: | 1. Bioinformatics Centre (BIF), PG and Research Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India;2. Computer Aided Drug Design and Molecular Modelling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India;3. Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India |
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| Abstract: | The recognition of DNA by small molecules is of special importance in the design of new drugs. Many natural and synthetic compounds have the ability to interact with the minor groove of DNA. In the present study, identification of minor groove binding compounds was attained by the combined approach of pharmacophore modelling, virtual screening and molecular dynamics approach. Experimentally reported 32 minor groove binding compounds were used to develop the pharmacophore model. Based on the fitness score, best three pharmacophore hypotheses were selected and used as template for screening the compounds from drug bank database. This pharmacophore‐based screening provides many compounds with the same pharmacological properties. All these compounds were subjected to four phases of docking protocols with combined Glide‐quantum‐polarized ligand docking approach. Molecular dynamics results indicated that selected compounds are more active and showed good interaction in the binding site of DNA. Based on the scoring parameters and energy values, the best compounds were selected, and antibacterial activity of these compounds was identified using in vitro antimicrobial techniques. Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | molecular dynamics MIC pharmacophore modelling QM/MM docking Staphylococcus aureus |
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