Computational and experimental analysis of short peptide motifs for enzyme inhibition
Journal Article - Open Access
Rutgers University-Camden Camden United States
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The metabolism of living systems involves many enzymes that play key roles as catalystsand are essential to biological function. Searching ligands with the ability to modulateenzyme activities is central to diagnosis and therapeutics. Peptides represent a promisingclass of potential enzyme modulators due to the large chemical diversity, and well-establishedmethods for library synthesis. Peptides and their derivatives are found to play criticalroles in modulating enzymes and mediating cellular uptakes, which are increasingly valuablein therapeutics. We present a methodology that uses molecular dynamics MD andpoint-variant screening to identify short peptide motifs that are critical for inhibiting beta-galactosidasebeta-Gal. MD was used to simulate the conformations of peptides and to suggestshort motifs that were most populated in simulated conformations. The function of the simulatedmotifs was further validated by the experimental point-variant screening as critical segmentsfor inhibiting the enzyme.