In-silico endogenic substrate prediction study of Cytochrome P450 1B1 (CYP1B1)

Abstract

Cytochrome P450 1B1 (CYP1B1) belongs to cytochrome P450 monooxygenases superfamily and is one of the CYP1 family isoforms, which actively take part in the metabolism of various xenobiotics in the body. CYP1B1 is highly expressed in multiple human tissues, implied in various types of human cancers, but its intracellular function and role in various human pathologies are yet to be understood entirely. In this regard, research in the past two decades has yielded sufficient information about its structure, amino acid sequence, and interaction with various xenobiotics, including pro-carcinogens. One aspect that remains hard to pin down is the information regarding the endogenic substrates of this protein. The scope of the present study is to predict the endogenic substrates (metabolic products of either arachidonic acid or cholesterol) of CYP1B1 with high binding affinity characteristics. We performed in-silico screening for these endogenic compounds with CYP1B1 protein modes to find best binding affinity, atomic contact energy (ACE) and score values. A total of thirteen compounds showed the highest binding affinity with CYP1B1. We found that leukotriene E4, leukotriene A4, Deoxycholic acid, tetrahydrocortisone showed highest ACE values and other substrate binding characteristics, making them excellent candidates for validation by laboratory experiments.