Peptide macrocycles possess characteristics that make them ideal as drug candidates, molecular recognition elements, and a variety of other applications involving their unique interactions with proteins. Computational analysis of these peptide macrocycle-protein interactions is useful for elucidating details that help underscore the true differences between peptide macrocycle binding candidates and facilitate the design of improved binders. The following protocol is useful for computational screening and analysis of a series of peptide macrocycle candidates binding to a protein target with a known structure but unknown binding site. It uses readily available open source software and is suitable for High Performance Computing.
Keywords: Binding free energy; MM/GBSA; Molecular dynamics; Peptide–protein interactions.
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