Unveiling Dynamic Hotspots in Protein-Ligand Binding: Accelerating Target and Drug Discovery Approaches

揭示蛋白质-配体结合中的动态热点:加速靶点和药物发现方法

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Abstract

Computational methods have transformed target and drug discovery, significantly accelerating the identification of biological targets and lead compounds. Despite its limitations, in silico molecular docking represents a foundational tool. Molecular Dynamics (MD) simulations, employing accurate force fields, provide near-realistic insights into a compound's behavior within a biological target. However, docking and MD predictions may be unreliable without precise knowledge of the target binding site. Through MD simulations, we investigated 100 co-crystal structures of biological targets complexed with active compounds, identifying key structural and energy dynamic features that govern target-ligand interactions. Our analysis provides a detailed quantitative description of these parameters, offering critical validation for improving the predictive reliability of docking and MD simulations. This work provides a robust framework for refining early-stage drug discovery and target identification.

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