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Updated: Jan 30, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Mechanistic enzymology in drug discovery: a fresh perspective
Geoffrey A Holdgate1, Thomas D Meek2, Rachel L Grimley1
1Discovery Sciences, IMED Biotech Unit, AstraZeneca, Building 310, Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
Abstract:
Given the therapeutic and commercial success of small-molecule enzyme inhibitors, as exemplified by kinase inhibitors in oncology, a major focus of current drug-discovery and development efforts is on enzyme targets. Understanding the course of an enzyme-catalysed reaction can help to conceptualize different types of inhibitor and to inform the design of screens to identify desired mechanisms. Exploiting this information allows the thorough evaluation of diverse compounds, providing the knowledge required to efficiently optimize leads towards differentiated candidate drugs. This review highlights the rationale for conducting high-quality mechanistic enzymology studies and considers the added value in combining such studies with orthogonal biophysical methods.
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