Modeling life processes at the molecular and subcellular levels

What is Computational Molecular Biophysics?

Biological processes are conducted at multiple temporal and spatial scales and are tightly regulated by the cell. Computational Molecular Biophysics focuses on fundamental and modulated processes at the subcellular and cellular levels. Many of these processes rely on molecular machines that conduct mechanical work, transmit timely signals, transport material across boundaries of compartments and execute biochemical reactions. Our research is firmly rooted in Hamilton’s equations of motions and statistical mechanics. These fundamental physical laws underpin computer simulations based on novel algorithms and theories developed to understand, predict and manipulate these processes at the atomistic level. We then conduct these simulations and test the predictions with experimental groups.

Current research areas

Examples of current research areas:

The mechanism of drug–kinase interactions

Protein kinases participate in many signaling processes, and their malfunction may cause diseases like cancer. Since there are many different kinases, it is hard to design a drug molecule that is specific to a particular pathway while also avoiding side effects. We study the drug-kinase interaction to understand the specificity of drug molecules. A success story is the drug ‘Imatinib’ that binds preferably to Abl kinase.

Cell-Penetrating Peptides

Cell-Penetrating Peptides (CPP) are small molecules that efficiently cross membrane barriers into cells and between compartments. We model the permeation process and consider the natural and synthetic design of these permeation agents.

Protein sliding along DNA

To read, synthesize and repair, protein machines slide along DNA. We point out the critical role counter ions play in the sliding process.

The operation of the Anthrax toxin

The anthrax toxin is a protein complex. It consists of a channel that enables the translocation of a protein called the Lethal Factor (LF) to the cytosol. Once in the cytosol, the LF causes significant damage. We model the translocation of the LF and use our Milestoning theory to conduct the simulations.

Working with partners

Current partnerships include collaborations with the Department of Chemistry and Department of Neuroscience at UT’s College of Natural Sciences, and with external groups and experts from University of Missouri, University of Rome, Sapienza, and the Hebrew University of Jerusalem.