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.

Rigid residue scan method for exploring hidden space of protein

Hidden space

Allostery is a fundamental dynamics property of many proteins, and plays a critical role in protein functions. Our goal is to develop effective computational tools to systematically evaluate significance of individual residue in protein dynamics and allostery without any a priori knowledge about protein allosteric mechanism. We developed rigid residue scan (RRS) method, in which systematic rigid-body molecular dynamics is carried out to quantify the contribution of each residue to the overall protein dynamics. Modification of individual residues may significantly affect the overall protein dynamics through the collective influence of residues on the protein’s structure. We demonstrated that applying RRS method could help to explore hidden conformational space of protein which is related to protein allosteric regulation.

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.

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 Prof. 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.