Computational methodologies are becoming indispensable techniques to determine chemical and biological reaction mechanisms and to provide structural and functional insight that is critical for further biomedical and pharmaceutical development. Our research emphasizes both methodology development and their applications to solve real world chemistry and biology problems.

Methodology Development in Free Energy Simulation

Free Energy Surface

As the most important thermodynamic quantity, free energy helps us to understand how chemical and biological species react, recognize and associate with each other. The development of methodology to calculate this quantity (actually the difference of free energies associated with different states) remains as one of the most active research fields in molecular modeling. Given certain order parameters as reaction coordinates, one could construct related free energy profile. But higher order reaction coordinates from complex chemical and biological systems pose great challenges in free energy calculation. We are utilizing the recent theoretical and technical advances in molecular mechanics to develop novel free energy calculation methods.

Nitric oxide (NO) Redox Cell Signaling Mechanisms


NO is a critical cell signaling messenger in the immune, cardiovascular and nervous systems. Due to its high reactivity and toxicity as a free radical, NO possesses a controversial effect on cell viability. The S-nitrosylation of protein thiol groups is a key mechanism in NO redox signal transduction, and lends a mechanistic basis for NO as a cell regulator. Numerous experiments have shown that the rate-limiting step of S-nitrosylation is NO autoxidation, independent of thiol concentration. Due to the transient nature and structural variety of reactive nitrogen species, very little is known about the mechanisms of either NO autoxidation or S-nitrosylation. Through the collaboration with clinical scientists, we strive to apply advanced computational methods to reveal the NO cell signaling mechanisms to answer mechanistic questions regarding this fundamental process in cell biology.

Computational Enzymology


The human body comprises about three trillion cells divided into more than 200 cell types. Each cell has many things to do at any given moment. All of the functions carried out by a cell are ultimately carried out by enzymes. With structures and functions determined for more and more enzymes, the bottleneck in enzymology is revealing the reaction mechanisms of each known enzyme to promote further applications, such as structure based drug design and bioengineering. The developing methods in computational biology and chemistry and ever growing computer power provide great opportunities to study the enzymatic mechanisms through computer simulations. Using chain-of-state reaction path methods, we are conducting intensive calculation on high performance computing (HPC) facilities to investigate the inhibiting mechanism of beta-lactamases by its novel inhibitors.

(Three scientists who did pioneer research to develop the main computational method to simulate enzymatic reactions, so called hybrid quantum mechanical and molecular mechanical (QM/MM) method, were awarded Nobel prize in chemistry in 2013 “for the development of multiscale models for complex chemical systems”.)

Please visit the website of the Computational and Theoretical Chemistry Group (CATCO) directed by Profs. Dieter Cremer and Elfi Kraka for more computational research carried out in the Chemistry Department.

Visit SMU Center for Scientific Computation for more people doing computational research and ongoing computational research projects at SMU.

Our research group is also part of SMU Center for Drug Discovery, Design, and Delivery (CD4). Find out more CD4 research projects.