(12b) Computational Exploration of Peptide Hydrolysis By Serine Protease: Combined Reaction Path and Process Variable Analysis
AIChE Annual Meeting
Sunday, November 10, 2019 - 3:48pm to 4:06pm
Our results will focus upon the computational study of serine protease activity. In this study, the Gibbs free energy of activation (Îgâ¡cat), rate coefficient (k), and the Gibbs free energy of reaction (ÎGrxn) were calculated using QM(EVB)/MM and free-energy perturbation (FEP)/umbrella sampling methods. These key thermochemical and kinetic parameters were utilized for detailed reaction path analysis on peptide bond cleavage with more than hundred numbers of samplings; Gibbs free energy surfaces of reaction were developed for reaction in water and in the native enzyme, also in noncatalyzed condition. Furthermore, influence of key environmental variables affecting catalysis such as temperature and pH were also analyzed, which can present paramount importance in process optimization for commercialized enzymes or for the scale-up of promising enzyme candidates. Moreover, key amino acid residues in the native enzyme active site were mutated to determine overall effects on catalytic activity. These learnings will be discussed in the context of enzyme design.
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