Biophysical Newsletter - June 2014

15

BIOPHYSICAL SOCIETY NEWSLETTER

2014

JUNE

Postdoc Spotlight GUISHAN ZHENG Harvard University Martin Karplus Lab

Q: In what field is your PhD? How did you specialize in biophysics? My PhD is in computational chemistry. As a graduate student, I was extremely interested in applying computational techniques to understand chemistry at the atomic level, especially those not feasible experimentally. As I learned more and more about computational chemistry, I realized there are even more interesting and challenging problems in biophysics, which are still waiting to be resolved or answered. Thus, I decided to pursue my postdoc in a computational biology lab. Q: What initially attracted you to the field? The development of QM/MM method has been shown to be able to accurately describe chemistry in biological systems. This inspired me to apply the method to study biological phenomena. I was especially interested in how enzymes achieved their catalytic power in cells. This is one typical problem that the QM/MM method can be ap- plied to to understand the unknown mystery of enzyme catalysis. Q: What is your current research project? I am currently studying how the “perfect” catalysis (catalysis whose rate is only limited by diffusion) is achieved by triosephosphate isomerase. I’ve been able to show the detailed reaction mechanism of this well-known glycolytic enzyme and identi- fied the origin of its efficiency using free energy simulations. This is the first time it was possible to use free energy simulations with the QM/MM potential for the study, for which I’ve improved the parameters of the QM method (i.e. density functional tight binding method) and developed a novel extended Lagrangian molecular dynamics with my collaborators.

Q: What skills and experiences have you gained/do you hope to gain from your postdoc position? As a postdoc working in Professor Karplus’ lab, I’ve learned to use free energy simulation tech- niques combined with the QM/MM potential and/or force fields to understand enzyme ca- talysis and protein conformational changes. I’m immensely grateful to Professor Karplus for his constant support and encouragement. Q: Tell us about a great experience or op- portunity you’ve had in the past year? Last year, I was able to publish our research on the understanding of the Bohr effects of hemoglobin using the computational titration method in Bio- chemistry . The research clarifies the origin of Bohr effect at the atomic level, which supplements the canonical Perutz model. Martin Karplus, Guishan’s PI says: Guishan Zheng is an outstanding postdoctoral fel- low, who is unusual in the computation community because he has made contributions to both quantum mechanical methodology and applications of model- ling to important problems. One of the latter is the first detailed test, verification, and extension of Perutz’s model for the Bohr effect. Although the proposal was made by Perutz in the 1970s, it is only now that it could be studied at the atomic level. Guishan has also introduced a method for speeding up QM/MM calculations and applied it to do the first free energy surface exploration of the critical enzyme triosephosphate isomerize and compared it with the reaction in solution.

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