Molecular Dynamics, Docking and Prediction of Absorption, Distribution, Metabolism and Excretion of Lycopene as Protein Inhibitor of Bcl2 and DNMT1

Abstract

Docking has been used currently in the early development of a drug candidate and a useful tool to predict the absorption, distribution, metabolism, and excretion (ADME) properties. Lycopene shows the strongest antioxidant activity among carotenoids, and has anticancer activity. This study predicts the ADME and simulates the docking of lycopene to predict the binding to the B-cell lymphoma 2 (Bcl2) and DNA (cytosine-5)-methyltransferase 1 (DNMT1) proteins in cancer cells. The computational method was conducted using pkCSM and SWISS ADME applications, and Gnina software to simulate lycopene docking to the proteins. Results show that lycopene has a molecular weight > 500, partition coefficient (log P) > 5, with a limited aqueous solubility, low skin permeability, however shows a good intestinal permeability and an active uptake through the blood brain barrier, the Convolutional Neural Network (CNN) Pose Score in protein Bcl2 of 0.7843, and DNMT1 score of 0.1279. Lycopene is predicted to have an interaction with Bcl2. There is a pi-alkyl interaction with amino acids PHE63 and TYR67, and a Pi-Sigma interaction with amino acid TYR161. ARG66, ALA108, LEU96, MET74, and VAL92 are among the amino acids that exhibit alkyl-alkyl interactions. Homology modelling was implemented due to the presence of a gap in the sequence within the chain, specifically between residues 31 and 49. The stability of lycopene-substrate interactions was evident during 20 ns molecular dynamics simulations, indicating its consistent behavior over the duration.