Drug Discovery Computational Chemistry Consultant

Expertise

• Scientific research and management records for the pharmaceutical industry:
• Inventor of a preferred method in the industry for LogP calculation
• 3D-QSAR method
• Pharmacophore modeling
• A quantitative definition of drug like molecules
• Potent anticancer compounds.
• Provide computational chemistry and chem- and bio- informatics problem solving for drug discovery.
• Computer aided drug discovery: Developed and led computational chemistry, cheminformatic laboratories in industrial or academic environments.
• Ligand binding modes and affinities of organic molecules for protein targets.
• Utilizing state-of-the-art molecular modeling and chemoinformatics packages; Schrodinger/maestro, DS/CHARMm, Pipeline Pilot, Knime, DFT, semiempirical, an initio MO and computer code development using FORTRAN, C and graphics languages.
• Cheminformatics
• Molecular Modeling
• Ligand docking
• Physicochemical Properties
• CNS-TEMPO
• Druggability Score

Experience

Undisclosed Company, Chief Consultant, Present

• Setup and maintain a low cost, state-of-the-art computational chemistry facility.
• Create web sites.
• Collect all public domain computational chemistry, cheminformatics and bioinformatics software.

Teva Brand Products, West Chester, PA, Computational Chemist, 2012 - 2018

• Set up and maintain a computational chemistry laboratory with 3D graphics and provide computational support to various ongoing therapeutic projects.
• Several projects produced clinical candidates.
• Setup and maintain a low cost, state-of-the-art computational chemistry facility.
• Provide computational chemistry support to all the (small molecule) drug discovery projects.
• The status of the projects varied from High Throughput Screening (HTS) data analysis to identify the best lead, to early stage lead optimization where enhancing the potency against the target was the main objective, to late stage lead optimization, where improving the ADMET properties with a minimum change of the target potency was the main objective.
• Developed a scoring scheme to differentiate CNS from non-CNS drugs.

Cephalon, West Chester, PA Senior Research Scientist, 2004 - 2011

Head of Computational Chemistry

• Set up and maintain a computational chemistry laboratory and provide computational support to various ongoing therapeutic projects.
• Acquired and integrated Linux cluster, Windows server, high end 3D graphics terminals to run computational chemistry software and database packages; Schrodinger/Maestro, Accelrys DS/Pipeline Pilot, Tripos/Sybyl, kinase inhibitors database, and GPCR ligand database etc.
• Developed the internal code of a chemoinformatics package (HypoTest) for automating the physicochemical property computation and therapeutic project dependent analysis of the properties, in collaboration with the research IT group.
• Crated protocols and acquired approximately 500,000 kinase and GPCR biased ligands.
• Designed and docked ALK/FAK kinase inhibitors for anticancer drug discovery in collaboration with the project chemists.
• The docking study was initially done on internally developed homology model and later on the available Xray structure.
• The approach helped to develop an excellent type I (DFG-in) clinical candidate.
• Developed pharmacophore models and did virtual screening using such models and physicochemical property profiles for CNS GPCR and amino acid transporters targets.
• This process led to a clinical candidate for H3 receptor.
• Designed and docked BRAF kinase inhibitors for anticancer drug discovery in collaboration with Ambitbio.
• The docking study was initially done on internally developed homology model and later on the available X-ray structure.
• The approach helped to develop a type II (DFG-out) clinical candidate.
• Designed and docked AXL kinase inhibitors for anticancer drug discovery in collaboration with the project chemists. The docking study was done on internally developed homology models.
• The approach helped to develop several excellent type II (DFG-out) preclinical inhibitors.
• Develop a CNS drug discovery technology.

Locus Discovery, Blue Bell, PA, Senior Research Scientist, 2002 - 2004

• Implement physicochemical property calculation and evaluation platform.
• Design and evaluate ligands for the ongoing therapeutic projects.
• Developed physicochemical and ADME property profiles of orally bio-available drugs.
• Applied Glide docking program, ADME property profile and Locus' proprietary fragment based drug design programs for P38 kinase drug design. The process led to identify several potent type II (DFG-out) P38 ligands.

Amgen, Thousand Oaks, CA, 1995 - 2002

Research Scientist III, 2000 - 2002
Research Scientist II, 1995 - 2000

• Installed the acquired hardware and software and provide computational chemistry support to the ongoing therapeutic projects. %u2022 Developed a model for PEGylated G-CSF.
• This project led to the approval of Pegfilgrastim (Neulasta).
• Used protein structured based design, docking and evaluation for CDK2/CDK5 inhibitors. It produced several potent preclinical candidates.
• Worked on the Calcium receptor project that led to the approval of Cinacalcet for treating hyperparathyroidism.
• Developed and implemented a 3D pharmacophore generation and virtual screening protocol.
• Developed physicochemical profiles of drug-like molecules and drug subclasses. It was useful in the generation of a drug-like combinatorial library and excellent calcium receptor inhibitors.
• Edited a very successful book on computational chemistry for drug discovery.

AM Technologies, Malvern, PA, Founding Member, 1994 - 1995

• Made available personal drug discovery codes for commercialization.
• Designed and developed a general-purpose drug design and molecular modeling package, Galaxy-AM2000 by integrating the proprietary codes.

Sterling-Winthrop, Collegeville, PA Senior Research Investigator,1990 - 1994

• Novel computational methods development and provided computational chemistry support to various therapeutic discovery projects.
• Developed a very reliable pharmacophore modeling method (DHYDM: Distance HYperspace Distance Measurement) to predict the pharmacophore geometry and the active conformation of protein ligands.
• Developed a fast computational method (PC-QSAR: Protein Cavity Quantitative Structure Activity Relationships) for the prediction of binding free energies of ligands for a target protein using the X-ray crystallographic protein-ligand complex structure and statistics.
• Successfully designed several highly potent preclinical matrix metalloproteinase inhibitors.
• Successfully designed several highly potent human elastase inhibitors.

Nucleic Acid Research Institute, Costa Mesa, CA, 1987 - 1990

Head, Department of Molecular Modeling

• Developed computational drug discovery methodologies and provide computational supports for the therapeutic discovery projects.
• Developed a novel 3D-QSAR methodology and computer software (REMOTEDISC).
• Improved AlogP and AMR parameters.
• Applied the 3-D QSAR technique to model the receptor site for certain antiviral nucleosides which led to the approval of Ribavirin.
• Applied the 3D-QSAR technique to model receptor site of several antitumor nucleosides.

University of Michigan, College of Pharmacy, Ann Arbor, MI Research Investigator 1985 -1987

• Introduced atomic hydrophobicity (ALOGP) and refractivity parameters for biological receptor mapping using 3-D QSAR technique and molecular similarity analysis.
• AlogP became one of the most extensively used methods for octanol-water partition coefficient calculation.
• Authored a chapter on research in Comprehensive Medicinal Chemistry text book.

Texas A&M University, Department of Chemistry, College Station, TX, 1981 - 1985

Assistant Research Scientist

• Improved distance geometry method for receptor modeling considering conformationally flexible ligands.
• Developed the first 3-D receptor cavity model for rat liver dihydrofolate reductase to account for diverse types of inhibitors.
• The model could not only explain the biological data of a large variety of inhibitors, but successfully predicted it for a large number of ligands.
• Developed a protocol for generating multiple distance matrices of a flexible molecule for geometry comparisons.

Honors & Publications

Credentials

• Post-Doctoral -, Computational Medicinal Chemistry, at the University of Michigan
• Chemistry-1st Class 1st, Gold Medalist, National Scholar, North Bengal University, Darjeeling, WB, India.
• SF, 1st Div. National Merit Scholar, WB Board of Secondary Education, Calcutta, WB, India

Languages

• Bengali
• Hindi

Academic and Professional Affiliations

• American Chemical Society
• American Association for the Advancement of Science
• New York Academy of Sciences

Publications and Patents

• Author of various publications; book chapters, text books, peer reviewed journals
• Over 90 research articles
• Over 30 presentations, many invited
• Domestic and international presentations
• One World patent

Education

• Ph.D. Medicinal-Computational Chemistry, Dept. of Pharmacy, Jadavpur University, Calcutta, India
• MSc. Organic Chemistry-1st Class 2nd, Gold Medalist, North Bengal University, Darjeeling. India
• BSc. Chemistry (With Honors) North Bengal University, Darjeeling, WB, India