A5016757143- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Synthesis and biological activity
- Wnt/β-catenin signaling in development and cancer
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Mosquito-borne diseases and control
- Machine Learning in Materials Science
- Influenza Virus Research Studies
- Neurobiology and Insect Physiology Research
- Genomics and Chromatin Dynamics
- Click Chemistry and Applications
- Bioactive Compounds and Antitumor Agents
- Axon Guidance and Neuronal Signaling
- DNA and Nucleic Acid Chemistry
- Biotin and Related Studies
- Drug Transport and Resistance Mechanisms
- Research on Leishmaniasis Studies
- PI3K/AKT/mTOR signaling in cancer
- Estrogen and related hormone effects
- Microbial Metabolic Engineering and Bioproduction
- Synthesis and Characterization of Heterocyclic Compounds
Biocon (India)
2024
Bristol-Myers Squibb (India)
2024
Biocon (Switzerland)
2024
Bristol-Myers Squibb (Germany)
2024
Fox Chase Cancer Center
2020-2023
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2016-2018
Alagappa University
2011-2015
Proteolysis-targeting chimaeras (PROTACs) are molecules that combine a target-binding warhead with an E3 ligase-recruiting moiety; by drawing the target protein into ternary complex ligase, PROTACs induce degradation. While hold exciting potential as chemical probes and therapeutic agents, development of PROTAC typically requires synthesis numerous analogs to thoroughly explore variations on linker; without extensive trial error, it is unclear how link two protein-recruiting moieties promote...
The sesquiterpenoid juvenile hormone (JH) is vital to insect development and reproduction. Intracellular JH receptors have recently been established as basic helix-loop-helix transcription factor (bHLH)/PAS proteins in Drosophila melanogaster known germ cell–expressed (Gce) its duplicate paralog, methoprene-tolerant (Met). Upon binding JH, Gce/Met activates target genes. Insects possess multiple native homologs whose molecular activities remain unexplored, diverse synthetic compounds...
Phosphoinositide-dependent kinase-1 plays a vital role in the PI3-kinase signaling pathway that regulates gene expression, cell cycle growth and proliferation. The common human cancers include lung, breast, blood prostate possess over stimulation of phosphoinositide-dependent making an interesting therapeutic target oncology. A ligand-based pharmacophore atom-based 3D-QSAR studies were carried out on set 82 inhibitors PDK1. six point with two hydrogen bond acceptors (A), three donors (D) one...
Tankyrases (TNKS) belong to the poly(ADP-ribose)polymerase (PARP) protein super family and play a vital role in Wnt/β-catenin signaling pathway. TNKS is potential target for therapeutic intervention against various cancers, heritable diseases (e.g. cherubism) implications replication of herpes simplex virus (HSV). The recent discovery structure with an IWR1 inhibitor has provided insight into binding modes which are specific will aid development drugs that protein. current study investigates...
Tankyrase 1 and 2 (TNKS) are promising attractive therapeutic targets in anticancer drug development. Herein, we report the findings of structure- ligand-based virtual screening for novel TNKS1 inhibitors using iterative rounds silico studies subsequent biological evaluation methods. Upon three compound databases, a final set five molecules were selected experimental validation. In order to prove our findings, tankyrase activity was assessed by calorimetric assay with identified lead...
Abstract PROTACs are molecules that combine a target-binding warhead with an E3 ligase-recruiting moiety; by drawing the target protein into ternary complex ligase, induce degradation. While hold exciting potential as chemical probes and therapeutic agents, development of PROTAC typically requires synthesis numerous analogs to thoroughly explore variations on linker; without extensive trial error, it is unclear how link two protein-recruiting moieties promote formation productive complex....
Molecular dynamics (MD) simulation is a powerful tool for characterizing ligand-protein conformational and offers significant advantages over docking other rigid structure-based computational methods. However, setting up, running, analyzing MD simulations continues to be multi-step process making it cumbersome assess library of ligands using MD. We present an automated workflow that streamlines Desmond simulations. The takes pre-docked protein structure as input, sets up runs with each...
Glioblastoma multiforme (GBM) is considered to be the most common and often deadly disorder which affects brain.It caused by over expression of proteins such as ephrin type-A receptor 2 (EphA2), epidermal growth factor (EGFR) EGFRvIII.These 3 are potential therapeutic targets for GBM.Among these, EphA2 reported over-expressed in ~90% GBM.Herein we selected 35 compounds from marine actinomycetes, 5 vitro vivo studied drug candidates 4 commercially available drugs GBM were identified...
In this study, a 5-point pharmacophore model was developed and the used to generate predictive atom-based 3D quantitative structure activity relationship (3D-QSAR) analysis for studied dataset of 50 compounds. The obtained 3D-QSAR shows correlation coefficient (R2) 0.87 training set compounds excellent power (Q2) 0.81 cross-validated test External validation indicated that our has high with values 0.99 0.65, respectively. most active least were further optimized using density functional...
The extreme surge of interest over the past decade surrounding use neural networks has inspired many groups to deploy them for predicting binding affinities drug-like molecules their receptors. A model that can accurately make such predictions potential screen large chemical libraries and help streamline drug discovery process. However, despite reports models predict quantitative inhibition using protein kinase sequences inhibitors' SMILES strings, it is still unclear whether these...
The existing H1N1 (2009) swine flu is pandemic in nature and responsible for global economic losses fatalities. Among the eight gene segments of H1N1, hemagglutinin (HA) plays a major role attachment virus to host cell surface entry viral RNA into leads infection. In this study, sequence phylogenetic analysis HA, from Mexico City along with 1952 sequences, different subtypes influenza A were studied results showed that closest relationship strain was (2007) Mallard Norway strain. Analysis...
ABSTRACT Artificial multidomain proteins with enhanced structural and functional properties can be utilized in a broad spectrum of applications. The design chimeric fusion utilizing protein domains or one‐domain miniproteins as building blocks is an important advancement for the creation new biomolecules biotechnology medical However, computational studies to describe detail dynamics geometry two‐domain constructs made from structurally functionally different are lacking. Here, we tested...
Abstract Cyclin-dependent kinase 9 (CDK9) plays a key role in transcription elongation, and more recently it was also identified as the molecular target of series diaminothiazole compounds that reverse epigenetic silencing phenotypic assay. To better understand structural basis underlying these compounds’ activity selectivity, we developed comparative modeling approach describe herein. Briefly, this draws upon strong conservation across active conformation all protein kinases, their shared...
The pharmacophore modeling and 3D-QSAR studies were performed on a series of amino alkyl rupestonates (Rupestonic Acid) derivatives reported for H1N1, H3N2 Influenza B virus, NA inhibition. In order to improve the efficacy derivatives, four point model with one acceptor three hydrophobic regions was developed. Furthermore, generated based hypothesis (AHHH) each subtype. more significant R2=0.9204, Q2=0.917 R2=0.8911, Q2=0.8905 R2=0.8385, Q2=0.7043 virus. results provided an invaluable...