Novel quantum mechanics based engineering approach enables transaminase to convert bulky ketone substrates

Conference Dates

September 24-28, 2017


Amine transaminases (ATAs) are being used in the production of chiral amines as an alternative to chemical synthesis to reduce cost and inadequate stereoselectivity. Yet, ATAs are enzymes, difficult to engineer because of the unique structural architecture of the active site that limits bulkier substrates, example Sitagliptin. However, in recent yearscombination of computational techniques and protein engineering has evolved enzymesto acceptbulkier substrates as shown for (R) 1 and more recently (S)-selective ATAs2. In this study, we have used the(S)-selective ATA from Chromobacterium violaceum to expand its substrate scope towards bulky ketones using a novel quantum mechanics (QM) based engineering framework. The framework predicts hotspots by analyzing the E-S molecular dynamics (MD) and QM simulations using novel methods developed in-house. To mention a few, path predictor, which predicts the path taken by the substrate to enter the active site, a grid based per residue energy profiling and atomistic motional correlations of the active site residues and QM based alanine scanning method.

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