BIOPHYSICAL SOCIETY NEWSLETTER
15
JUNE
2014
Postdoc Spotlight
GUISHAN ZHENG
Harvard University
Martin Karplus Lab
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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.
