Exploring the structure characteristics and major channels of cytochrome P450 2A6, 2A13, and 2E1 with pilocarpine.

The majority of cytochromes P450 play a critical role in metabolism of endogenous and exogenous substrates, some of its products are carcinogens. Therefore, inhibition of P450 enzymes activity can promote the detoxification and elimination of chemical carcinogens. In this study, molecular dynamics (MD) simulations and adaptive steered molecular dynamics (ASMD) simulations were performed to explore the structure features and channel dynamics of three P450 isoforms 2A6, 2A13, and 2E1 bound with the common inhibitor pilocarpine.

Studying the recognition mechanism of TcaR and ssDNA using molecular dynamic simulations.

The transcription regulator teicoplanin-associate locus regulator (TcaR) plays a vital role in interfering with ssDNA replication and resisting ssDNA phage invasion. Although recent studies demonstrated that TcaR had strong interaction with ssDNA, the dynamics and interaction mechanism of dimeric TcaR bound to ssDNA have not been rationalized at the atomic level. In our study, MD simulations combined with MM-GB/SA calculations were employed to study recognition mechanism between TcaR and ssDNA.

Investigation of ligand selectivity in CYP3A7 by molecular dynamics simulations.

Cytochrome P450 (CYP) 3A7 plays a crucial role in the biotransformation of the metabolized endogenous and exogenous steroids. To compare the metabolic capabilities of CYP3A7-ligands complexes, three endogenous ligands were selected, namely dehydroepiandrosterone (DHEA), estrone, and estradiol. In this study, a three-dimensional model of CYP3A7 was constructed by homology modeling using the crystal structure of CYP3A4 as the template and refined by molecular dynamics simulation (MD).

Structural features and dynamic investigations of the membrane-bound cytochrome P450 17A1.

Cytochrome P450 (CYP) 17A1 is a dual-function monooxygenase with a critical role in the synthesis of many human steroid hormones. The enzyme is an important target for treatment of breast and prostate cancers that proliferate in response to estrogens and androgens. Despite the crystallographic structures available for CYP17A1, no membrane-bound structural features of this enzyme at atomic level are available.