Structure-Based Approaches for the Prediction of Alzheimer's Disease Inhibitors: Comparative Interactions Analysis, Pharmacophore Modeling and Molecular Dynamics Simulations

Due to its significant role in neurodegeneration, Cyclin-dependent kinase 5 (CDK5) has emerged as a potential target for addressing neuropathological disorders, including Alzheimer's disease (AD). The application of CDK5 inhibitors has demonstrated promise in the treatment of AD. This prompted us to model this interesting target using a computational workflow named Docking-based Comparative Intermolecular Contacts Analysis (dbCICA). Approaches including 3D-QSAR, genetic algorithm, and pharmacophore modeling were employed to discover new CDK inhibitors. Exploring the frontier of Alzheimer's research, we identify novel inhibitors for CDK5, a key player in neurodegeneration. Using in silico drug design methods, including Comparative Interactions Analysis (dbCICA), Pharmacophore Modeling, and Molecular Dynamics, we reveal five promising anti-CDK5 hits. Our In silico studies on ADME, DFT and toxicity provide a glimpse into the future of Alzheimer's treatment. image