Detection of farnesyltransferase interface hot spots through computational alanine scanning mutagenesis.
作者： Marta AS Perez , Sérgio F Sousa , Eduardo FT Oliveira , Pedro A Fernandes , Maria J Ramos
DOI: 10.1021/JP205481Y
关键词:
摘要: In this study, we present a detailed characterization of the full α/β interface in farnesyltransferase (FTase) enzyme, an important target drug design efforts. This is presented terms hot spots, warm and null spots based on application improved variation computational alanine scanning mutagenesis methodology, complemented with extensive solvent-accessible surface area interfacial hydrogen-bonding analysis. A total 130 amino acid residues were considered analysis, number that represents 16.0% 814 enzyme. Globally, results provide clues most structural energetic determinants for dimer formation, suggesting several key targets at subunit development new molecules aim to inhibit FTase activity through blocking formation fully active dimer, yielding useful indications future
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