My research specialization includes Bioinformatics, Structural Biology, X-ray Crystallography, and Rational Structure Based Drug Design. My research currently focuses on clinically relevant gram-negative bacteria where I have pursued a multidisciplinary approach to understand the antibacterial resistance mechanisms. Experimental and computational methodology including genomic, proteomic and structural analysis have been adopted to understand the mechanisms responsible for antibiotic resistance as well as develop strategies to counter determinants of drug resistance and drug resistant pathogens. I am also extensively working towards determination of molecular interactions of antibiotic resistance proteins and identification of novel antimicrobial scaffolds to bypass antibiotic resistance by exploiting the structural knowledge about the various protein targets for the design of new antibiotics. The various Mur ligase pathway proteins have been characterized and identified as novel drug targets. The biochemically isolated proteins are being processed to design newer molecules as anti-typhoidal compounds. The bacterial protein, DNA Gyrase has been explored as a novel target site for development of antimicrobials. My research also involves whole genome sequencing as a tool for drug development and to elucidate novel resistance genes and resistance mechanisms in clinical isolates of bacterial pathogens.
My contributions in the structural biology and drug design projects include structure determinations of various proteins using the tools of X-ray Crystallography (i) Dimeric form of peptidoglycan recognition protein involved in innate cell immunity of action and complexes with various ligands to establish its role as antibacterial agent (ii) lactoperoxidase from various sources and its complexes with different ligands and ions to establish its mechanism of action (iii) a new family of mammary gland proteins - signaling glycoproteins from different (iv) first dimeric disintegrin, a strong integrin antagonist, for design of synthetic anti-coogulant agents (v) ribose inactivating proteins which are involved in plant defence from different plants (vi) several phospholipase A2s from diverse sources, their native as well as co-complexed structures with natural and designed inhibitors and design of potent inhibitors as strong drug candidates against arthritis and inflammation These extensive structural studies have led to a number of lead molecules which were designed against diseases such as inflammation, cancer and microbial infections. In addition to these macromolecular structures, I have contributed to the development of design rules using alpha, beta dehydro-residues for designing specific conformations of peptides. Research interests in bioinformatics include identification of novel targets for drug development, protein homology modeling, molecular docking and virtual screening and detection of lead molecules, identifying the structural basis of diseases due to point mutations and development of databases related to proteins/genes implicated in disorders/cancers.
- Gupta D, Tiwari P, Haque MA, Sachdeva E, Hassan MI, Ethayathulla AS, Kaur P. (2021) Structural insights into the transient closed conformation and pH dependent ATPase activity of S.Typhi Gyrase B N- terminal domain. Arch Biochem Biophys. Apr 15;701:108786. doi: 10.1016/j.abb.2021.108786.
- Gupta D, Sharma P, Singh M, Kumar M, Ethayathulla AS, Kaur P. (2021) Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants. Cell Mol Life Sci. 78:7967-7989. doi: 10.1007/s00018-021-04008-0. (Review)
- Tripathi MK, Nath A, Singh TP, Ethayathulla AS, Kaur P (2021) Evolving scenario of big data and Artificial Intelligence (AI) in drug discovery Mol Divers 25(3):1439-1460. doi: 10.1007/s11030-021-10256-w.
- Katiyar A, Kaur G, Rani L, Jena L, Singh H, Kumar L, Sharma A, Kaur P*, Gupta R*. (2021) Genome-wide identification of potential biomarkers in multiple myeloma using meta-analysis of mRNA and miRNA expression data. Sci Rep. 11(1):10957. doi: 10.1038/s41598-021-90424-y. (Co-Corresponding authors)
- Singh PK, Pandey S, Rani C, Ahmad N, Viswanathan V, Sharma P, Kaur P, Sharma S, Singh TP (2021) Potassium-induced partial inhibition of lactoperoxidase: structure of the complex of lactoperoxidase with potassium ion at 2.20 Å resolution. J Biol Inorg Chem. 26(1):149-159. doi: 10.1007/s00775-020-01844-6.
- Singh PK, Sharma P, Bhushan A, Kaur P, Sharma S, Singh TP. (2021) Structure of a ternary complex of lactoperoxidase with iodide and hydrogen peroxide at 1.77 Å resolution. J Inorg Biochem. 220:111461. doi: 10.1016/j.jinorgbio.2021.111461.
- Sharma P, Vijayan V, Pant P., Vikram N, Kaur P, Singh, TP, Sharma S (2021) Identification of potential drug candidates to combat COVID-19: a structural study using the main protease (mpro) of SARS-CoV-2. J. Biomol Struct Dyn 39(17):6649-6659.
- Vijayan V, Pant P., Vikram N, Kaur P, Singh, TP, Sharma S, Sharma P (2021) Identification of promising drug candidates against NSP16 of SARS-CoV-2through computational drug repurposing study. J. Biomol Struct Dyn 39(17):6713-6727.
- Gupta A, Vijayan V, Pant P., Kaur P, Singh, TP, Sharma P, Sharma S (2021) Structure prediction and discovery of inhibitors against phosphopanthothenoyl cysteine synthetase of Acinetobacter baumannii. J. Biomol Struct Dyn Aug 4:1-13.
- Singh M, Malhotra L, Haque MA, Kumar M, Tikhomirov A, Litvinova V, Korolev AM, Ethayathulla AS, Das U, Shchekotikhin AE, Kaur P. (2021)Heteroarene-fused anthraquinone derivatives as potential modulators for human aurora kinase B. Biochimie. 182:152-165. doi: 10.1016/j.biochi.2020.12.024.
- Viswanathan V, Rani C, Ahmad N, Singh PK, Sharma P, Kaur P, Sharma S, Singh TP.(2021) Structure of Yak Lactoperoxidase at 1.55 Å Resolution. Protein J. 40: 8-18. doi: 10.1007/s10930-020-09957-2. .PMID: 33389415
- Koley T, Madaan S, Chowdhury SR, Kumar M, Kaur P, Singh TP, Ethayathulla AS. (2021) Structural analysis of COVID-19 spike protein in recognizing the ACE2 receptor of different mammalian species and its susceptibility to viral infection. 3 Biotech.11(2):109. doi: 10.1007/s13205-020-02599-2. Epub 2021 Feb 1.PMID: 33552834
- Malhotra L, Goyal HKV, Jhuria S, Dev K, Kumar S, Kumar M, Kaur P, Ethayathulla AS. (2021) Curcumin rescue p53Y220C in BxPC-3 pancreatic adenocarcinomas cell line: Evidence-based on computational, biophysical, and in vivo studies. Biochim Biophys Acta Gen Subj. 1865:129807. doi: 10.1016/j.bbagen.2020.129807.
- Gupta A, Singh PK, Sharma P, Kaur P, Sharma S, Singh TP. (2020) Structural and biochemical studies of phosphopantetheine adenylyltransferase from Acinetobacter baumannii with dephospho-coenzyme A and coenzyme A. Int J Biol Macromol. 142:181-190. doi: 10.1016/j.ijbiomac.2019.09.090. ]
- Gupta A, Rani C, Pant P, Vijayan V, Vikram N, Kaur P, Singh TP, Sharma S, Sharma P. (2020) Structure-Based Virtual Screening and Biochemical Validation to Discover a Potential Inhibitor of the SARS-CoV-2 Main Protease.ACS Omega. 5:33151-33161. doi: 10.1021/acsomega.0c04808. ]
- Naz F, Mashkoor M, Sharma P, Haque MA, Kapil A, Kumar M, Kaur P, Abdul Samath E.(2020) Drug repurposing approach to target FtsZ cell division protein from Salmonella Typhi. Int J Biol Macromol. 159:1073-1083. doi: 10.1016/j.ijbiomac.2020.05.063. ]
- Sachdeva, E., Kaur, G., Tiwari, P., Gupta, D, Singh TP, Ethayathulla, AS, Kaur P. (2020). The pivot point arginines identified in the β-pinwheel structure of C-terminal domain from Salmonella Typhi DNA Gyrase A subunit. Sci Rep 10, 7817 https://doi.org/10.1038/s41598-020-64792-w]
- Tripathi MK, Singh P, Sharma S, Singh TP, Ethayathulla AS, Kaur P (2020) Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor J. Biomol Struc. Dyn. doi.org/10.1080/07391102.2020.1790425]
- Katiyar A, Sharma P, Dahiya S, Singh H, Kapil A, Kaur P (2020) Genomic profiling of antimicrobial resistance genes in clinical isolates of Salmonella Typhi from patients infected with Typhoid fever in India. Sci. Rep. 10:8299. doi: 10.1038/s41598-020-64934-0.]
- Sharma P, Vijayan V , Pant P, Sharma M, Vikram N, Kaur P, Singh TP, Sharma S (2020) Identification of potential drug candidates to combat COVID-19: a structural study using the main protease (mpro) of SARS-CoV-2 J. Biomol Struc. Dyn. doi.org/10.1080/07391102.2020.1798286
- Bansal R Haque MA, Hassan MI, Ethayathulla AS, Kaur P. (2020) Structural and conformational behavior of MurE ligase from Salmonella enterica serovar Typhi at different temperature and pH conditions Int J Biol Macromol. 150:389-399. doi: 10.1016/j.ijbiomac.2020.01.306
- Tiwari A, Kumar M, Kaur P, Kumar B, Sagi SSK (2020) Efficacy of Quercetin as a potent sensitizer of β2 AR in combating the impairment of fluid clearance in lungs of rats under hypoxia. Respiratory Physiology & Neurobiology 273: 103334
- Verma D, Gupta S, Saxena R, Kaur P, Srivastava S, Gupta V. (2020) Allosteric inhibition and kinetic characterization of Klebsiella pneumoniae CysE: An emerging drug target. Int J Biol Macromol. 151:1240‐1249. doi:10.1016/j.ijbiomac.2019.10.170
- Kumar A, Jain V, Chowdhury MR, Kumar M, Kaur P, Kabra M. (2020) Pathogenic/likely pathogenic variants in the SHOX, GHR and IGFALS genes among Indian children with idiopathic short stature. J Pediatr Endocrinol Metab 33:79-88. doi: 10.1515/jpem-2019-0234.
Recent Chapter in Book
1. Tripathi, MK, Sharma, S, Singh, TP, Ethayathulla, AS, Kaur P (2021) Computational Intelligence in Drug Repurposing for COVID-19 in 'Computational Intelligence Methods in COVID-19: Surveillance, Prevention, Prediction and Diagnosis" in the series Studies in Computational Intelligence', Pg 273 - 294 Ed. Khalid Raza Springer Singapore
online. Link: https://www.springer.com/gp/book/9789811585333