Journal article

HARP: a database of structural impacts of systematic missense mutations in drug targets of Mycobacterium leprae

Sundeep Chaitanya Vedithi, Sony Malhotra, Marcin J Skwark, Asma Munir, Marta Acebron-Garcia-De-Eulate, Vaishali P Waman, Ali Alsulami, David B Ascher, Tom L Blundell

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL | ELSEVIER | Published : 2020

Abstract

Computational Saturation Mutagenesis is an in-silico approach that employs systematic mutagenesis of each amino acid residue in the protein to all other amino acid types, and predicts changes in thermodynamic stability and affinity to the other subunits/protein counterparts, ligands and nucleic acid molecules. The data thus generated are useful in understanding the functional consequences of mutations in antimicrobial resistance phenotypes. In this study, we applied computational saturation mutagenesis to three important drug-targets in Mycobacterium leprae (M. leprae) for the drugs dapsone, rifampin and ofloxacin namely Dihydropteroate Synthase (DHPS), RNA Polymerase (RNAP) and DNA Gyrase (..

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Grants

Awarded by American Leprosy Missions Grant, United States of America


Awarded by MRC DBT Grant, United Kingdom and India


Awarded by cystic fibrosis, Switzerland


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by Wellcome Trust Programme Grant, United Kingdom


Funding Acknowledgements

Authors would like to thank the rest of the computational biology team at the Department of Biochemistry, University of Cambridge, United Kingdom, for their overarching support and guidance in the data collection and analysis. SCV and MADGE were supported by American Leprosy Missions Grant, United States of America, (Grant No: G88726), SM was supported by the MRC DBT Grant, United Kingdom and India (RG78439), MJS was supported by a grant from Foundation Botnar working to support children with cystic fibrosis, Switzerland (Project 6063), DBA was funded by an Investigator Grant from the National Health and Medical Research Council (NHMRC) of Australia [GNT1174405] and by the Wellcome Trust Programme Grant, United Kingdom (200814/Z/16/Z) and supported in part by the Victorian Government's OIS Program, Australia. AFA is funded on a PhD Scholarship by the Kingdom of Saudi Arabia. AM was supported by a scholarship jointly funded by Pakistan Higher Education Commission (HEC) and Cambridge Commonwealth, European and International Trust (CCEIT) Scholarship. TLB was supported by the Wellcome Trust Programme Grant, United Kingdom (200814/Z/16/Z).