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oai:figshare.com:article/32630949 2026-10-01T17:23:45Z portal_1172 item_type_8 month_year_10_2026

Computational study on the selectivity of iron-containing hydroxylase Chenggong Hui (11068645) PUREID: 231866186 QMMM computational chemistry molecular dynamics DFT P450 Many Iron-containing hydroxylases have a high degree of regio- and diastereoselectivity and can be used as biocatalysts for producing specific chiral alcohols from un-active C-H sites. Here C-H functionalization catalyzed by Iron-containing heme and nonheme were studied, using cytochrome P450 and PtlH as examples. In this work, the C-H activation in the hydroxylation reaction of a model substrate artemisinin catalyzed by three selective P450BM3 variants was studied by combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations. A distinct linear correlation was observed between the barriers of C-H bond activation and the distances between Fe=O oxo and the hydrogen atom to be abstracted. These findings would provide valuable guidance for predicting the reactivity of P450BM3 and other similar reactions where hydrogen abstraction is the rate-limiting step. The second part of the project is the study on non-heme hydroxylase PtlH. In this section, a new descriptor ΔGCat Effi that is related to both the substrate binding affinity and activation barrier associated with the rate-limiting hydrogen abstraction step was proposed and tested. With current data, ΔGCat Effi showed promising result in explaining the selectivity in C-H activation and may be used to predict the selectivity of other iron-containing heme or non-heme enzymes. 2026-10-01T17:23:45Z Text Thesis 10.17034/32630949.v1 https://figshare.com/articles/thesis/Computational_study_on_the_selectivity_of_iron-containing_hydroxylase/32630949 All Rights Reserved