Multifaceted computational modelling in pharmaceutical research and development

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dc.check.date2025-09-30
dc.contributor.advisorTiana, Davide
dc.contributor.advisorLawrence, Simon
dc.contributor.authorVinay Kumar Reddy, Cheemarla
dc.contributor.funderSwiss Forum for International Agricultural Research
dc.contributor.funderNational Institute of Neurological Disorders and Stroke
dc.date.accessioned2024-06-17T13:32:52Z
dc.date.available2024-06-17T13:32:52Z
dc.date.issued2023en
dc.date.submitted2023
dc.description.abstractDrug development is a multi-step process and takes around 12 to 15 years for a new drug to get approved. In the current scenario, to accelerate the drug development process and to reduce the time frame, most pharmaceutical companies have in-house developed workflows comprised of a hybrid use of computational and experimental approaches. This thesis was focused on employing state-of-the-art molecular modelling methods in three significant areas of pharmaceutical research and development. This thesis comprises an introductory part (chapter 1) and a productive part (chapter 3 to chapter 5). The first chapter of this thesis is the literature review, outlining the foundational studies and research framework used in chapters 3 to 5. The second chapter describes the thesis structure and objectives of the other three chapters. The third chapter explores the hit identification process, utilising docking to screen a small database of phytopharmaceuticals against sclerostin protein followed by an investigation of the stability of the protein-ligand complexes through standard molecular dynamics and funnel meta dynamics. The fourth chapter involves the modelling of adsorption and diffusion of doxorubicin, paclitaxel, carboplatin, and gemcitabine anticancer drugs and also drug combinations such as doxorubicin with carboplatin, paclitaxel with gemcitabine and carboplatin employing NUIG-4 metal-organic framework as drug delivery agents. In this chapter, the comprehensive understanding of molecular interactions governing drug adsorption and diffusion was studied using Grand Canonical Monte Carlo (GCMC) and Molecular Dynamics (MD) simulations. The fifth chapter focuses on investigating the mechanism of chiral Bronsted acid catalysed asymmetric synthesis of homoallyl alcohols from ortho vinyl benzaldehydes and allyl boron pinacol ester using density functional theory methods (DFT), QTAIM, and NCI analysis. Furthermore, a comparative analysis of transition structures of Ortho vinyl and ortho alkynyl benzaldehyde substrates was studied.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationVinay Kumar Reddy, C. 2023. Multifaceted computational modelling in pharmaceutical research and development. PhD Thesis, University College Cork.
dc.identifier.endpage158
dc.identifier.urihttps://hdl.handle.net/10468/16014
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/NIH/NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE/271201200406P-5-0-1/US/DRUG DISCOVERY CONSULTING; SUPPORT- PROFESSIONAL: OTHER/
dc.rights© 2023, Cheemarla Vinay Kumar Reddy.
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectMolecular dynamics
dc.subjectPhytopharmaceuticals
dc.subjectDrug Diffusion
dc.subjectAnticancer drug delivery
dc.subjectMOFs
dc.subjectChiral drugs
dc.subjectDFT
dc.titleMultifaceted computational modelling in pharmaceutical research and development
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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