Computational Study of Membrane-inserted BAK

Abstract

The BAK protein is part of the BCL-2 protein family, a group that regulates intrinsic apoptosis. Research has shown that proteins that control apoptosis are linked to diseases such as cancer, Alzheimer's, and Parkinson’s, among many others. A key concept is that of molecular dynamics. A molecular dynamic is a computational simulation technique that allows molecules to interact. By using various force fields, we can calculate and visualize the movement of these molecules over time. This work has focused on the modelling of two systems, the BAK-BIM(BH3) complex and the BAK protein alone, inserted in a lipid membrane. These systems were allowed to evolve with molecular dynamics. With the information obtained from these simulations, we have been able to visualize the most stable conformations of BAK inserted in the membrane, which we then attempted to categorize. We also observed how the angle of insertion of the protein in the membrane changed. Finally, we looked for the possible binding sites of the protein. Understanding the behaviour of BAK in the membrane and finding possible allosteric binding sites, will allow us in the future to develop drugs that act as inhibitors or activators of the BAK protein