Stability and reactivity study of bio-molecules brucine and colchicine towards electrophile and nucleophile attacks: Insight from DFT and MD simulations

A set of molecular descriptors have been calculated and used in order to identify the most reactive parts of bioactive molecules, brucine (BRU) and colchicine (COL). Comparison of various physico-chemical properties has been performed in order to investigate stability. Besides global and local reactive parameters, attention has been paid to the autoxidation properties and reactivity with water molecules. Molecular Dynamics (MD) simulations and docking results show that BRU and COL bound D-lactate dehydrogenase enzyme are less fluctuating and more stable than the apo protein. To reveal the autoxidation and reactivity with water molecules Density Functional Theory (DFT) simulation has been carried out for the interactions and charge transfer mechanism of water molecules on different sites of bio-molecules, BRU and COL. This may help to further understand and identify the most active parts of the bio-molecules, BRU and COL. We have presented various interaction parameters, e.g., adsorption energy, molecular distance, charge transfer and orbital interactions. The sites with higher adsorption energy and charge transfer signify better reactivity with water. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A set of molecular descriptors and physico-chemical properties have been used to identify the most reactive parts and investigate stability of bioactive molecules brucine and colchicine. Molecular Dynamics simulations and Density Functional Theory simulations revealed that the bound complexes are more stable and have better reactivity with water molecules, providing a deeper understanding of the interactions and charge transfer mechanisms.