Molecular Dynamics as a Tool for Virtual Ligand Screening

Methods Mol Biol. 2024;2714:33-83. doi: 10.1007/978-1-0716-3441-7_3.ABSTRACTRational drug design is essential for new drugs to emerge, especially when the structure of a target protein or nucleic acid is known. To that purpose, high-throughput virtual ligand screening campaigns aim at discovering computationally new binding molecules or fragments to modulate particular biomolecular interactions or biological activities, related to a disease process. The structure-based virtual ligand screening process primarily relies on docking methods which allow predicting the binding of a molecule to a biological target structure with a correct conformation and the best possible affinity. The docking method itself is not sufficient as it suffers from several and crucial limitations (lack of full protein flexibility information, no solvation and ion effects, poor scoring functions, and unreliable molecular affinity estimation).At the interface of computer techniques and drug discovery, molecular dynamics (MD) allows introducing protein flexibility before or after a docking protocol, refining the structure of protein-drug complexes in the presence of water, ions, and even in membrane-like environments, describing more precisely the temporal evolution of the biological complex and ranking these complexes with more accurate binding energy calculations. In this chapter, we describe the up-to-date MD, which plays the role of supporting tools in the virtual ligand screening (VS) process.Without ...
Source: Methods of Information in Medicine - Category: Information Technology Authors: Source Type: research