Yingkai Zhang's Research Interests
We are interested in developing and applying novel computational and theoretical methods to understand the chemistry of important biological processes, including metalloenzyme catalysis, enzyme regulation, biomolecular recognition, DNA damage and repair. Due to the complexity of biological processes, the computational methods that we develop and utilize are multiscale in nature, ranging from electronic level description of crucial chemical bonds to coarse-grained approaches for large scale motions and interactions. Two specific examples of our research interest are:
Combined quantum mechanical/molecular mechanical method (QM/MM)
The main challenge for computational methods to study enzyme reactions come from two aspects: one is the large size of the biological system, usually containing at least thousands of atoms; the other is that the reaction involves chemical bond formation and breaking, which requires the explicit consideration of the electrons. The high level quantum mechanical method can describe chemical reactions quite well, but computationally too expensive to study the system with thousands of atoms. On the other hand, although the molecular mechanical method has been routinely used to study large systems such as proteins and DNA, it is unable to describe the bond formation and breaking process. A promising direction to go beyond these limitations is to combine these two methods together, which is called as QM/MM. In our group, we are interested in developing novel approaches to improve the accuracy and applicability of the combined ab initio QM/MM methods.
Simulation of metalloenzymes
Enzymes containing transition metals are often medically significant while posing special challenges for computational methods, with the main difficulty coming from the transition metal center and its ligand environment. In our group, we develop and apply novel computational methods to systematically study metalloenzymes. These studies are complement to experimental studies, and to provide detailed insight as well as a quantitative understanding of the inner workings of metalloenzymes, which will facilitate the rational-design of new useful ligands and novel enzymes.
The transition state of the methyl transfer reaction catalyzed by Histone Lysine Methyltransferase SET7/9 determined with B3LYP(6-31G*) QM/MM calculations