Title: Structure, evolution and virtual screening of NDM-1 strain from Kolkata

Authors: Ganesh Chandra Sahoo; Mukta Rani; Md. Yousuf Ansari; Chanda Jha; Sindhuprava Rana; Manas Ranjan Dikhit; Kanhu Charan Moharana; Rakesh Kumar; Pradeep Das

Addresses: BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam Kuan, Patna 800007, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam Kuan, Patna 800007, India ' Pharmacoinformatics Department, National Institute of Pharmaceutical Education and Research, Hajipur, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam kuan, Patna 800007, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam kuan, Patna 800007, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam kuan, Patna 800007, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam kuan, Patna 800007, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam kuan, Patna 800007, India ' BioMedical Informatics Division, Rajendra Memorial Research Institute of Medical Sciences, Agam kuan, Patna 800007, India; Pharmacoinformatics Department, National Institute of Pharmaceutical Education and Research, Hajipur, India

Abstract: β-lactam antibiotics are utilised to treat bacterial infection. β-lactamase enzymes (EC 3.5.2.6) are produced by several bacteria and are responsible for their resistance to β-lactam antibiotics like penicillin, cephamycins and carbapenems. New Delhi Metallo-β-lactamase (NDM-1) is a gene that makes bacteria resistant to β-lactam antibiotics. Preparing a compound against NDM-1 will require additional investment and development by drug manufacturers as the current antibiotics will not treat patients with NDM-1 resistance. NDM-1 of Kolkata showed convergent-type evolution with other NDM-1 producing strains. The modelled structure exhibited α-β-α barrel-type domain along with Zn metallo-β-lactamase N-terminal domain. Compounds belonging to cephalosporins (relatively resistant to β-lactamase) and other antibiotics ceftaroline, ceftobiprole, piperacillin, penamecillin, azidocillin, cefonicid, tigecycline and colistin have exhibited better binding affinity with the modelled NDM-1.

Keywords: NDM-1 structure; NDM-1 evolution; virtual screening; antibiotics; penicillin; cephamycins; carbapenems; NDM-1 resistance; threading; ceftaroline; ceftobiprole; piperacillin; penamecillin; azidocillin; cefonicid; tigecycline; colistin; alpha-beta-alpha barrel; cephalosporins; beta-lactamase enzymes; modelling.

DOI: 10.1504/IJBRA.2014.060761

International Journal of Bioinformatics Research and Applications, 2014 Vol.10 No.3, pp.235 - 263

Received: 06 Jul 2011
Accepted: 02 Jul 2012

Published online: 24 Oct 2014 *

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