Computational Structural Biology for Enzyme-Targeted Drug Design: Molecular Modeling and Docking Insights

Enzymes are central to physiological processes, and their dysfunction drives diseases like Alzheimer’s, where acetylcholinesterase (AChE) dysregulation impairs synaptic function. Designing enzyme inhibitors is a cornerstone of drug discovery, requiring precise and efficient methodologies. This review explores computational structural biology’s role in enzyme-targeted drug design, emphasizing molecular modeling, docking, and dynamics simulations. Techniques such as homology modeling, active site prediction, and virtual screening enable rapid discovery of novel AChE inhibitors with high affinity for the enzyme’s active site gorge. Tools like MODELLER, AutoDock, and GROMACS facilitate accurate structural predictions and dynamic analyses, as demonstrated in case studies optimizing inhibitors like donepezil for Alzheimer’s treatment. Challenges, including conformational flexibility and docking inaccuracies, persist computationally efficiency but advancements in machine learning, enhanced sampling, and cryo-EM offer solutions. Integrating computational and experimental methods promises innovative therapeutics for neurodegenerative diseases.

کلیدواژه ها:

Computational Biology ، Molecular Docking ، Molecular Dynamics ، Acetylcholinesterase Inhibitors ، Enzyme-Targeted Drug Design ، Structural Bioinformatics