Curriculum Vitae
Jianping Lin
Address
1001 Arcadia Ave. #2
Arcadia, CA 91007
Email: jianpingl@gmail.com
Phone: 626-241-6163
Education
2000.8 – 2005.8
Ph.D.
Advisor:
Duke University, Durham, NC
in Theoretical Biophysics and Biochemistry
Prof. David N. Beratan
1997.8– 2000.7
M.S.
Advisor:
Beijing University, Beijing, China
in Polymer Chemistry
Prof. Gaoyuan Wei
1992.8 – 1997.7
B.S.
Beijing University, Beijing, China
in Chemistry
Advisor:
Prof. Gaoyuan Wei
Working Experience
2006.3Research Fellow City of Hope National medical Center
2005.9-2006.2 Research associate
Duke University
2001.9-2005.8 Research Assistant
Duke University
2001.5-2001.8 Research Assistant
University of Pittsburgh
2000.8-2001.4 Teaching Assistant
University of Pittsburgh
1997.8-2000.7 Research Assistant
Beijing University
1992.8-1997.7 Undergraduate Research
Beijing University
Techniques
Molecular Dynamics, essential dynamics
Brownian Dynamics, Monte Carlo
Gaussian Network Model
Virtual Ligand Screening and post analysis
Software Skills
Gaussian 98
UHBD, Sybyl
NAMD, VMD
Maestro 8 (including GLIDE, PRIME, INDUCE-FIT DOCK)
Workshop Attended
•
Summer school on theoretical and computational biophysics: Computational
approaches for simulation of biological systems (June 2-13, 2003)
Organizer: Professor Klaus Schulten, Beckman Institute, University of Illinois
• Research workshop and summer school on theory and computation in molecular
biological physics (August 9-20, 2004)
Organizer: Professor Charles L Brooks III, Department of Molecular Biology, the
Scripps Research Institute.
Curriculum Vitae
Research Experiences
Molecular dynamics simulations of insertion of chemically modified DNA
nanostructures into water-chloroform interface
DNA based 2D and 3D arrays have been used as templates for synthesis of functional
polymers and proteins. Hydrophobic or amphiphilic DNA arrays would be useful for the
synthesis of hydrophobic molecules. The objective of this study is to design modified
amphiphilic double crossover DX-DNA molecule that would insert into waterchloroform interface thus showing amphiphilic character. Since experiments for such
design are tedious, we have used molecular dynamics simulations to identify and
optimize the functional groups to modify the DNA backbone, that would enable insertion
into the water-chloroform interface, prior to synthesis. By methylating the phosphates of
the backbone, to make phosphonates, combined with placing a benzyl group at the 2’
position of the deoxyribose rings in the backbone, we observed that the simple B-DNA
structure was able to insert into the water-chloroform interface. We find that the transfer
free energy of the methylated benzylated DNA is better than either just methylated or
benzylated DNA. The driving force for this insertion comes from entropic contribution to
the free energy and the favorable van der Waals interaction of the chloroform molecules
with the methyl and benzyl groups of the DNA. (Accepted by Biophysical Journal, 2008).
Molecular dynamics simulations of the conformational changes in Signal
Transducers and Activators of Transcription, Stat1 and Stat3
All Signal Transducers and Activators of Transcription (STAT) factors are a family of
cytoplasmic transcription factors that mediate the signal response to cytokines, growth
factors, and hormonal factors. The activation of Stat3, a member of the STAT family, has
been found to be elevated in a large number of diverse human cancers. It is pertinent to
understand the dynamics of the dimer interface to enable Stat3 dimer inhibitor design. To
this end, we performed 50 ns MD simulations for Stat3 dimer, and its closely related
member of the family, Stat1 dimer in explicit water. We observed a large scale domain
motion in Stat3 dimer while the structure of the monomer remains intact. The driving
force for this conformational change is enhanced binding of the Stat3 dimer to the DNA,
thereby promoting transcription. Our model shows that the carboxy terminus of one
monomer wraps around the core of the SH2 domain of the other monomer, and this
region that makes up the dimer interface remains intact during the dynamics. Water
diffuses into a cavity under this interface thus expanding a pre-existing cavity that gets
gated and closed by the loops in the SH2 domain. This cavity serves as a potential
binding pocket for inhibitor design. (Submitted to J. Am. Chem. Soc. May, 2008)
Design of inhibitors for signal transduction and activator of transcription (STAT3)
by targeting new binding sites
We first performed 2.6 ns molecular dynamics on Stat3 crystal structure. For the
equilibrated structure, we performed virtual ligand screen for the binding site right under
Jianping Lin
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Curriculum Vitae
the crossover (This is the first research to target this site) between two c-terminal of
STAT3 dimer from Sequeonom database. We pick the top10% ligands from GLIDE
score. Using our own filter strategy, we narrow down the number of ligands to 437.
Among the 437 ligands, our collaborators pick 52 ligands to test in the inhibition of DNA
binding for STAT3 and found one compound can inhibit the binding at IC50 <= 30 μM in
EMSA (electrophoretic mobility shift assay). And it is proven to have specificity for
STAT3 instead of Stat1 and no toxicity to normal cell. This compound could be anticancer drug with specificity by targeting STAT protein. The results will be included into a
manuscript in preparation (to be submitted to Cell) and a patent to be applied.
The solvent effect on inter-protein electron transfer
We explore the distance dependence of electronic coupling between redox
cofactors, mediated in part by water, as two redox proteins approach. Rather than
describe the ET rate decay with a single exponential parameter, we employ explicit
electronic structure calculations and find three distinct tunneling mediation regimes: a
conventional protein-mediated regime near protein-protein contact, a “structured water”
regime with soft distance dependence for small protein-protein gaps, and a bulk water
regime with a rapidly decaying coupling at larger distance. We use this analysis to
predict the rate for cytochrome b5 electron self-exchange. These results are published in
Science.
Simulation of electron transfer between cytochrome c2 and the bacterial
photosynthetic reaction center
In bacterial photosynthesis, electron transfer from a cytochrome to the special
pair of the reaction center completes the cycle of converting light into chemical energy.
We used Brownian dynamics to compute the second-order electron transfer rate,
between cytochrome c2 and bacterial photosynthetic reaction center. The results
compare well with the experimental kinetic results. We also predict that the second-order
electron transfer rate decreases with increasing ionic strength, a characteristic of
electrostatically controlled docking. We predict that double mutations of the system can
switch the mechanism between activation & diffusion control. These results are
published in J. Phys. Chem. B.
Simulation of tunneling through flexible molecules in scanning tunneling
microscopy
Since electron-tunneling interactions are exponentially sensitive to geometry
changes, thermal fluctuations are expected to have a large influence on roomtemperature tunneling currents and scanning tunneling microscopy (STM) images. Our
analysis of STM currents follows the approach of Marcus and co-workers. We use this
strategy to explore current variation among specific molecular conformations from which
we compute the conformationally averaged currents for several fixed tip-to-substrate
distances. We simulate the process of pulling a octanedithiol molecule from a “random
coil” to a fully extended form. We find that the tunneling current is expected to have a
strong conformational dependence. The predicted tunneling currents in the saturated
structures decrease approximately exponentially with distance as the structure are
extended. This observation is consistent with a rule that “strong conformers win”. The
results are published in J. Phys. Chem. A.
The cooperative motion of ATPase
Jianping Lin
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Curriculum Vitae
Adenosine triphosphate (ATP) chemical-bond energy drives large-scale
conformational changes in proteins. H+-ATPase pumps protons in the plasma membrane
to maintain the intracellular pH and membrane potential. To understand the molecular
mechanism of proton pumping, we are using a coarse-grained strategy (normal mode
analysis with a Gaussian network model) and essential dynamics to analyze the
cooperative motion of the ATPase. We use molecular dynamics and Brownian dynamics
methods to explore H+ transport through the ion channel.
Publications
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Jianping Lin; Nadrian C. Seeman; Nagarajan Vaidehi “Molecular dynamics
simulations of insertion of chemically modified DNA nanostructures into waterchloroform interface” Accepted by Biophysical Journal in April, 2008.
James C. Sung; Jianping Lin Diamond Nanotechnology: Synthesis and applications
Pan Stanford Publishing, in press.
Jianping Lin; Nagarajan Vaidehi “Molecular dynamics simulations of the
conformational changes in Signal Transducers and Activators of Transcription, Stat1
and Stat3” Submitted to J. Am. Chem. Soc. In May, 2008.
Jianping Lin; Ralf Buettner; Richard Jove; Nagarajan; et al. “A novel inhibitor for
transduction and activator of transcription (STAT3) by targeting new binding site“ In
preparation ( to be submitted to Cell, 2008).
Jianping Lin; Ilya A. Balabin; David N. Beratan “The Nature of Aqueous Tunneling
Pathways between Electron-transfer Proteins”
Science 2005, 310,1311-1313.
related news: “Water can ease electron transfer between proteins” Chemical &
Engineering News November 28, 2005. Page 11.
Jianping Lin; David N. Beratan “Simulation of Electron transfer between
Cytochrome c2 and the Bacterial Photosynthetic Reaction Center: Brownian
Dynamics Analysis of the Native Proteins and Double Mutants.” J. Phys. Chem. B
2005, 109, 7529-7534.
Jianping Lin; David N. Beratan "Tunneling while Pulling: The Dependence of
Tunneling Current on End-to-End Distance in a Flexible Molecule." J. Phys. Chem.
A 2004, 108, 5655-5661.
Spiros S. Skourtis; Jianping Lin; David N. Beratan “The Effects of Bridge Motion on
Electron Transfer Reactions Mediated by Tunneling” Chapter 18 in Modern Methods
for Theoretical Physical Chemistry of Biopolymers. Edited By E. B. Starikov; S.
Tanaka; J. P. Lewis, Elsevier Press, June 2006.
Awards
 Outstanding Student Award of Beijing University (1995-1996)
 Outstanding Graduate Award of Beijing University (1998-1999)
Presentation
• Jianping Lin; Iyla A. Balabin; David N. Beratan “Interprotein Electron Transfer
through Aqueous Pathways” APS meeting in Los Angeles, March, 2005.
Jianping Lin
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