Abstract

PHARMACOPHORE-BASED DRUG DESIGN: BRIDGING MOLECULAR INSIGHTS AND THERAPEUTIC INNOVATIONS

Mr. Tushar B. Gajjar*, Mr. Harshil Patel and Mr. Viswam Modi

ABSTRACT

Pharmacophore modelling is a crucial approach in computer-aided drug design (CADD) that facilitates the identification and optimization of new therapeutic agents. This review article synthesizes the fundamental principles, methodologies, and advancements in pharmacophore modelling, highlighting its significance in the drug discovery process. The introduction defines a pharmacophore as the ensemble of steric and electronic features necessary for molecular recognition of a ligand by a biological macromolecule. Ligand-based pharmacophore modelling involves analysing known active compounds to derive a model that captures the essential features required for biological activity. This process includes data setpreparation, feature identification, and virtual screening. Structure-based pharmacophore modelling integrates molecular docking simulations with pharmacophore modelling, considering the spatial arrangement of pharmacophoric features in relation to the target binding site. Pharmacophore modelling has found extensive applications beyond initial screening, such as ADME-Tox predictions, side effect and off-target prediction, and target identification. Recent advancements include the development of user-friendly software tools that simplify the process of pharmacophore generation and analysis. Despite its advantages, pharmacophore modelling is not without limitations. The effectiveness of a pharmacophore model depends on the quality and diversity of the training set, and its application is challenging when no structural information is available for the target or ligands. Future research is expected to focus on integrating pharmacophore modelling with machine learning techniques to enhance predictive accuracy and broaden its applicability in complex biological systems. In conclusion, pharmacophore-based drug design represents a critical intersection of chemistry and computational science, driving innovation in drug discovery. By leveraging the principles of pharmacophore modelling, researchers can efficiently navigate the vast chemical space, identifying promising drug candidates while minimizing the associated costs and time. As computational techniques continue to evolve, the role of pharmacophores in drug design is poised to expand, offering new avenues for therapeutic development.

Keywords: Pharmacophore Modeling, Virtual Screening, Ligand-Based Pharmacophore, Structure-Based Pharmacophore, Computational Drug Design.