PhD Research · Computational Biology · Drug Discovery

शोधकौशलम्

डॉक्टरल् शोधात् जैवसूचनाशास्त्रीयशुष्कप्रयोगशालाकौशल्यम्

Research Focus

Bridging computational and experimental cancer research — from AI-driven drug discovery pipelines (SieveAI) and molecular dynamics simulations (coarse-grain MARTINI for membranes, atomistic CHARMM36 for proteins) to cell-based validation assays. Specializing in protein-ligand docking, protein-protein interactions, structure prediction (AlphaFold2, SwissModel, I-TASSER, Rosetta), MMPBSA binding free energy, and exosomal miRNA analysis. Automated workflows from PDB preparation through docking, MD, and result extraction — reducing months of manual work to hours.

जैवसूचनाशास्त्रम् सङ्गणकीयजीवविज्ञानम् च

सङ्गणकीयऔषधआвиष्कारे, आण्विकगतिकज्ञाने, अनुवंशिकीयदत्तांशविश्लेषणे, पाइपलाइनविकासे च विस्तृतानुभवः। बहुओपन्सोर्सोपकरणानि निर्मितानि प्रकशितानि च।

Protein-Ligand Docking

औषध-लक्ष्य-बन्धनस्य पूर्वानुमानाय आण्विक-बन्धनम् (Molecular docking) — AutoDock Vina, SwissDock, तथा PATCHDOCK इत्येतषां उपयोगं कृत्वा सहस्राणि यौगिकानि परीक्षितवान् तथा च कर्क-लक्ष्याणाम् (यथा CXCL9/10 तथा SKP2) कृते सम्भाव्य-चिकित्सा-प्रत्याशिनः चिह्नितवान्।

  • AutoDock Vina — batch protein-ligand docking (1,950+ complexes)
  • Protein-protein docking — HADDOCK, pyDockWeb, PatchDock, ClusPro
  • Protein-protein interaction — CD151 cholesterol binding, TWIST1-OGT/OGase, survivin-caspase complexes
  • Protein-complex docking — ternary systems (survivin + OBPHA + caspase-3/7/9)
  • Peptide-peptide docking — TWIST1-OGT/OGase interactions
  • Ligand preparation — AutoDockTools, OpenBabel, PubChemPy 3D SDF, SwissParam topology
  • Post-docking analysis — ChimeraX H-bond/contact automation, PLIP, PRODIGY
  • Cancer targets — CXCL9/10, SKP2, PPARγ, BRCA1, GRK2, CD63-VEGF, p53, Bcl-2, PDGFR
  • DrugBank & FDA drug screening — 8K+ conformers, immune checkpoints (CD28, TIGIT, PD-1)

Molecular Dynamics Simulation

प्रोटिन-स्थायित्वस्य, लिगण्ड-बन्धन-गत्याः, तथा नैनोसेकण्ड-समयमानयोः संरचनात्मक-परिवर्तनानां अध्ययनाय GROMACS तथा WebGro इत्येताभ्यां सह आण्विक-गतिकी-सिमुलेशनम् — बन्धन-भविष्यवाणीनां प्रमाणीकरणाय अतिमहत्त्वपूर्णम्।

  • GROMACS — full MD pipeline (pdb2gmx, editconf, solvate, genion, grompp, mdrun) up to 300ns
  • Coarse-grain MD — MARTINI force field for lipid–ligand membrane systems (Lapatinib/DMPC/cholesterol)
  • Atomistic MD — CHARMM36 force field for protein–ligand complexes; AMBER/CHARMM36 for membranes
  • CHARMM-GUI membrane builder — DMPC, DOPC, DOPS, cholesterol bilayer preparation & embedding
  • Desmond MD — local installation & WebGro cloud submission, trajectory analysis
  • MMPBSA — gmx_MMPBSA binding free energy calculations (300ns trajectories)
  • RMSD / RMSF / Rg / SASA / DSSP — protein stability, secondary structure, solvent analysis
  • SwissParam & PRODRG — ligand topology/ITP generation for GROMACS CHARMM force field
  • GMXvg — published GROMACS visualization & plotting tool

Protein Structure Prediction

AlphaFold2, SwissModel, I-TASSER, Rosetta च — प्रोटीन-संरचनापूर्वानुमानम्, म्यूटेंट-मॉडलिंग, ट्रांसमेम्ब्रेन-पूर्वानुमानम्, प्रोटीन-तुलना (RMSD) च।

  • AlphaFold2 — protein structure prediction via Google Colab (IL27 complex, CD151, CD63)
  • SwissModel — homology modeling + QA (quality assessment) for mutant proteins (3EQH-ALA76GLY)
  • I-TASSER — 3D structure prediction for membrane & transmembrane proteins
  • Rosetta — protein structure prediction and design
  • Avogadro — energy minimization of small molecules & ligand 3D optimization
  • Protein structure comparison — ChimeraX Matchmaker (RMSD, primary/secondary/tertiary structure)
  • PDB processing — UniProt mapping, PDBTM for transmembrane, chain cleanup, HETATM separation
  • O-GlcNAcylation site prediction — YinOYang, dbPTM, PhosphoSitePlus for GRK2 sites (S20, S121, S370)
  • Membrane protein resources — PDBTM, TMDock, MemProtMD, PerMemDB, MBPpred, ProteinTools

अनुवंशिकीयट्रान्सक्रिप्टोमिक्स् च

GEOParse इत्यनेन सह GEO-दत्तांशसमूहानां विश्लेषणं, RNA-Seq तथा ncRNA-अभिव्यक्ति-रूपाणां अध्ययनं, कर्करोगे विसंगत-जीन्-नियामक-जालस्य च परिज्ञानाय मार्ग-संवर्धनं GO-टीकाकरणं च।

  • GEO dataset mining — GEOParse querying, GDS database search, sample/platform/series filtering (GSE15852, GSE73002, GSE77348)
  • Differential gene expression — PyDGE framework, MCF7 vs MCF10A, normal vs tumor expression analysis
  • TCGA cancer genomics — GDC portal data download (gdc-client), TCGA-BRCA miRNA-seq, TNBC cohort filtering, sample type codes
  • miRNA database consolidation — miRBase (2,693 mature), ExoCarta, EVmiRNA, miRCancer cross-referencing & Venn analysis
  • miRNA target prediction — TargetScan, miRDB, DIANA, miRWalk, miRTarBase validated targets
  • Exosomal miRNA analysis — miR-34a, miR-10b, miR-21, miR-9; ExoLoger prediction database
  • ncRNA analysis — lncRNA, circRNA, siRNA, piRNA; RNAComposer, UNAFold, MXfold2 for 3D structure
  • Pathway & network analysis — KEGG (KEGGScape), WikiPathways, Biocarta, STRING interaction networks, FunRich enrichment
  • NCBI/Entrez queries — PubMed search, GDS metadata extraction, Gene database cross-referencing
  • Cancer gene resources — IntOGen (BRCA driver genes), cBioPortal, OncoKB, COSMIC, CancerES (IIITD)
  • PTM databases — dbPTM, PhosphoSitePlus, O-GlcNAc (oglcnac.mcw.edu), VerSeDa

Drug Discovery Pipeline

SieveAI इति स्वचालित-औषध-अन्वेषण-पाइपलाइनं निर्मितवान् यत् समूहेषु परीक्षणं, बन्धनं, मूल्याङ्कनं च सञ्चालयति — yeन मासानां हस्तश्रमः होरासु परिवर्तितः। Zenodo DOI इत्यनेन सह प्रकाशितं तथा च मुक्तस्रोतरूपेण प्रदत्तम्।

  • SieveAI — end-to-end automated drug discovery pipeline: PDB prep → ligand prep → docking → result extraction → filtering
  • Bulk docking automation — 576 cancer genes × 5 ligands = 1,950+ complexes; 9,127 Vina results parsed & filtered
  • DrugBank high-throughput screening — GRK2 (3,894 complexes ~60h compute), immune checkpoints (8K+ conformers)
  • Automated PDB processing — Python scripts for ATOM/HETATM separation, chain cleanup, grid box calculation, PDBQT conversion
  • Bulk ligand preparation — AutoDockTools prepare_ligand4.py, OpenBabel batch PDB→SDF→SMILES, PubChemPy 3D SDF download
  • Automated result extraction — Vina score parsing, ChimeraX H-bond/contact command generation, best-pose selection by residue interaction
  • SwissADME bulk — automated SMILES submission, ADME radar scraping, property aggregation across 88+ compounds
  • MDDAA-Mate — docking analysis assistant for validation & cross-checking against published results

Bioinformatics Data Mining

PubMed-साहित्य-खननाय विशिष्ट-जाल-अपमार्जन-तन्त्राणि (scraping frameworks) विकसितानि, येन सहस्राणि संक्षेपेभ्यः वैज्ञानिक-जाल-स्रोतोभ्यः च व्यवस्थित-समीक्षाभ्यः संरचित-दत्तांशः निष्कासितः।

  • PubMed querying & full-text mining — biopubmed CLI tool
  • Scientific literature meta-analysis — systematic review automation
  • Web scraping framework (Scrapper) — GEO, DrugBank, UniProt, ZINC, PubChem data extraction
  • API integration — PubChemPy 3D SDF download, RCSB ligand fetch, KEGG KGML pathway
  • miR literature curation — exosomal miR article classification & filtering

Biomedical Text Mining

अनुसन्धान-संक्षेपेभ्यः नामाङ्कित-सत्ता-प्रत्यभिज्ञानस्य (NER) कीवर्ड-सह-उत्पत्ति-विश्लेषणस्य च कृते जैववैद्यकीय-NLP — विशालग्रन्थेभ्यः स्वचालित-साहित्य-संश्लेषणं परिकल्पना-निर्माणं च सक्षमं करोति।

  • Biomedical NLP — keyword co-occurrence, named entity recognition, spaCy POS/lemma extraction
  • Text mining — structured extraction from thousands of PubMed results
  • Exosomal miR prediction — NLP + clustering for unvalidated miR identification
  • Regex-based data extraction — SMILES conversion, gene ID mapping, UniProt batch queries

Machine Learning for Bioinformatics

SMILES/SMARTS-अङ्गुलीमुद्रा-उपयोगेन मेटाबोलाइट-वर्गीकरणाय गम्भीर-नाडी-जालानि (DNN), यत् रैंडम फ़ॉरेस्ट, SVM, तथा XGBoost प्रतिरूपैः दृढ-मूल्याङ्कनेन (AUC, F1, MCC) सह पूरितम् अस्ति।

  • DNN for metabolite classification — SMILES/SMARTS fingerprinting
  • Random Forest / SVM / XGBoost — cancer gene expression classifiers
  • Model evaluation — AUC, F1, MCC metrics
  • PCA & one-hot encoding — miRNA sequence analysis & dimensionality reduction

Research Software & Tools

सङ्गणकीय-सॉफ्टवेयर्-उपकरणानि रचितवान् प्रकाशितवान् च — SieveAI (औषध-अन्वेषणम्), ExoLoger (एक्सोसोमल miRNA-पूर्वानुमानम्), GMXvg (GROMACS दृश्यावलोकनम्, Zenodo DOI), miRvim (3D miRNA-संरचना-दत्तांशकोशः), तथा UtilityLib (पायथन्-उपयोगिताः, Zenodo DOI)।

  • SieveAI — automated drug discovery pipeline
  • ExoLoger — exosomal miRNA prediction database
  • GMXvg — GROMACS visualization & plotting
  • miRVim — 3D miRNA structure database
  • UtilityLib — Python utility library (PyPI v2.21.4)
  • TheBiomics — Drupal education platform (17K+ users)
  • biopubmed — PubMed scraping & processing CLI
  • Scrapper — scientific web data extraction framework
  • MDDAA-Mate — docking analysis assistant & validation tool
  • PyDGE — differential gene expression analysis framework

शुष्कप्रयोगशाला प्रयोगात्मकजीवविज्ञानम् च

कर्चरजीवविज्ञाने औषधविज्ञाने च कोशिकासंवर्धने, आण्विकजीवविज्ञानपरीक्षासु, प्रोटीनकार्ये, काचान्तर्गतअध्ययनेषु च प्रायोगिकानुभवः।

कोशिकासंवर्धनम् अनुरक्षणम् च

कठोर-पूतिबाध-रहित (aseptic) तन्त्रेण स्तनधारि-कोशिका-रेखाणां (MG63, MCF7, MM231, LN229) परिरक्षणं कृतवान् — यस्मिन् शीत-परिरक्षणं, उप-संवर्धनम्, प्रेषणम्, ट्रान्सफेक्शन-अनुकूलनम्, माइकोप्लाज्मा-परीक्षणं च अन्तर्भवति।

  • Mammalian cell culture — MG63, MCF7, MDA-MB-231, LN229, A549
  • Animal cell culture — aseptic technique, laminar flow hood, CO₂ incubator operation
  • Cell line maintenance — sub-culturing, passaging, cell counting (hemocytometer), viability assessment
  • Cryopreservation — liquid nitrogen storage, freeze-thaw recovery, DMSO cryoprotectant protocols
  • Transfection optimization — lipid-based and electroporation methods
  • Mycoplasma testing & contamination control
  • Cancer cell to adipocyte differentiation (PPARγ agonist studies)

प्रोटीनाकलनम् परीक्षाः च

प्रोटिन-मात्रा-निर्धारणं (Bradford, BCA), SDS-PAGE तथा वेस्टर्न ब्लॉटिंग् इत्येतेषां माध्यमेन पृथक्करणं प्रत्यभिज्ञानं च, तथा च ELISA तथा सह-प्रतिरक्षी-अवक्षेपणैः (co-immunoprecipitation) सह परस्परक्रिया-अध्ययनम्।

  • Protein estimation — Bradford & BCA assay (standard curve preparation)
  • SDS-PAGE & Western blotting — Vimentin, target protein detection
  • Wet blot transfer — tank transfer system for protein membrane immobilization
  • Dry blot transfer — semi-dry transfer for rapid protein detection
  • Gel Doc imaging — documentation & analysis of electrophoresis gels and blots
  • ELISA — quantitative protein interaction analysis
  • Co-immunoprecipitation — protein-protein interaction validation
  • A280 protein quantification

आण्विकजीवविज्ञानतन्त्राणि

मानक-आण्विक-जीवविज्ञान-कार्यप्रवाहः — TRIzol इत्यनेन सह RNA-निष्कर्षणम्, cDNA-संश्लेषणम्, जीन्-अभिव्यक्तये qPCR/RT-PCR, एगरोज़-जैल-वैद्युतकणसञ्चलनम्, तथा क्लोनिङ्ग्-प्राइमर-रूपरेखाभिः सह प्लास्मिड-पृथक्करणम्।

  • RNA extraction — TRIzol method
  • cDNA synthesis & gene expression analysis
  • RT-PCR & qPCR — reverse transcription, quantitative expression profiling
  • Agarose gel electrophoresis — nucleic acid separation & Gel Doc visualization
  • Plasmid isolation, cloning & primer design
  • Competent cell transformation

काचान्तर्गतअध्ययनानि

औषध-परीक्षणाय कोशिका-आधारित-परीक्षणाः — MTT/XTT व्यवहार्यता, वसा-निर्माणं, व्रण-निवारण-प्रवासनं, आक्रमण-परीक्षाः, एपोप्टोसिस-प्रत्यभिज्ञानं (Annexin V), तथा औषध-संयोजन-परस्परप्रवाहः (CI सूचकाङ्कः)।

  • MTT & XTT viability assays — dose-response drug screening, IC₅₀ determination
  • Colony formation assay — clonogenic survival quantification
  • Wound healing migration assay — scratch assay for cell motility
  • Invasion assays — transwell migration & Matrigel invasion
  • Apoptosis detection — Annexin V / PI staining
  • Drug combination synergy — Combination Index (CI) method
  • Cancer cell vs normal cell comparative studies

Instruments & Equipment

कोशिका-संवर्धन-आणविकजीवविज्ञान-प्रोटीनविश्लेषण-वर्णलेखन-कार्यप्रवाहायाः प्रयोगशाला-उपकरणानि उपस्कराः च।

  • Gel Doc system — gel documentation, blot imaging & densitometry analysis
  • CO₂ incubator — mammalian cell culture environment control
  • Laminar flow hood — aseptic technique & sterile workspace
  • Microplate reader — absorbance/fluorescence for MTT, Bradford, BCA, ELISA
  • Centrifuge — refrigerated & bench-top, cell pelleting, fractionation
  • PCR thermal cycler — RT-PCR & qPCR amplification
  • Electrophoresis apparatus — vertical SDS-PAGE & horizontal agarose gel
  • Wet & dry blot transfer systems — tank & semi-dry protein transfer
  • HPLC system — basic operation & familiarization with analytical chromatography devices

वर्णलेखनम् HPLC च

यौगिक-प्रत्यभिज्ञानाय शुद्धता-विश्लेषणाय च HPLC-सञ्चालनं पद्धति-विकासः च, सहैव स्तम्भ-तनुस्तर-वर्णलेखन-तन्त्राणि (column and thin-layer chromatography)।

  • Chromatography basics — column, thin-layer & basic HPLC familiarization
  • Column & thin-layer chromatography
  • Standard curve & peak integration