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2025-09-30 Tiana, Davide Lawrence, Simon Vinay Kumar Reddy, Cheemarla Swiss Forum for International Agricultural Research National Institute of Neurological Disorders and Stroke 2024-06-17T13:32:52Z 2024-06-17T13:32:52Z 2023 2023 Drug 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. Not peer reviewed Accepted Version application/pdf Vinay Kumar Reddy, C. 2023. Multifaceted computational modelling in pharmaceutical research and development. PhD Thesis, University College Cork. 158 https://hdl.handle.net/10468/16014 en University College Cork info:eu-repo/grantAgreement/NIH/NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE/271201200406P-5-0-1/US/DRUG DISCOVERY CONSULTING; SUPPORT- PROFESSIONAL: OTHER/ © 2023, Cheemarla Vinay Kumar Reddy. https://creativecommons.org/licenses/by-nc/4.0/ Molecular dynamics Phytopharmaceuticals Drug Diffusion Anticancer drug delivery MOFs Chiral drugs DFT Multifaceted computational modelling in pharmaceutical research and development Doctoral thesis Doctoral PhD - Doctor of Philosophyinfo:eu-repo/semantics/openAccess