Research Associate (Postdoc), 2005-2008

The Scripps Research Institute, Department of Molecular Biology, La Jolla, CA

Advisor: Prof. Arthur J. Olson

Website: mgl.scripps.edu

Project 6: Fragment-based lead discovery, protein-ligand docking, algorithm development

(collaborator: Prof. Charles D. Stout, X-ray crystallographer)

Developed a docking-based program to automate interpretation of X-ray density maps from fragment screening.

Applied the program to fragment cocktail screening of HIV protease.

Optimized preliminary hits theoretically through growth, linkage and substructure search.

Software:

MapDock – automated fitting of ligands on X-ray density maps to interpret ligand binding positions and conformations on proteins (Python; to be released).

Publication:

Zhang, Q., Stout, C.D., & Olson, A.J., “MapDock, a program for automated interpretation of X-ray density maps from fragment screening”, in preparation, 2010.

Perryman, A.L, Zhang, Q., Soutter, H.H., Rosenfeld, R., McRee, D.E., Olson, A.J., Elder, J.E., & Stout, C.D., “Fragment-Based Screen against HIV Protease”, Chemical Biology & Drug Design, in press, 2010.

A fragment (ball-and-stick) fit on a density peak (red outlined surface) in an X-ray density difference map from fragment cocktail screening on the HIV protease (surface and ribbon) using the ActiveSight Fragment Library.

Project 5: Signaling pathway, GPCR modeling, protein-peptide docking, molecular dynamics

(collaborator: Prof. Wolfram Ruf, biologist, department of immunology)

Built a homology model of protease-activated receptor PAR-2 and modeled its interactions with extracellular proteins to understand its signaling pathway.

Publication:

Zhang, Q., Petersen, H.H., Ruf, W., & Olson, A.J., “Molecular Dynamics Simulations and Functional Characterization of the Interactions of the PAR2 Ectodomain with Factor VIIa”, Proteins: Structure, Function, and Bioinformatics, 77: 559-569 2009.

Project 4: Protein-protein interaction, protein-protein docking, algorithm development

(collaborator: Prof. Michel Sanner, software developer)

Developed a multi-resolution Gaussian surface and studied the effects of surface smoothing on shape complementarity of protein-protein complexes.

Mentored one graduate student on developing an electrostatic scoring term for protein-protein docking.

Software:

ShapeFit – building multi-resolution Gaussian surfaces and performing protein-protein docking (contributed partially; Python).

Publication:

Zhang, Q., Sanner, M., & Olson, A.J., “Shape complementarity of protein-protein complexes at multiple resolutions”, Proteins: Structure, Function, and Bioinformatics, 75: 453-467, 2009.

Assistant Research Scientist (Postdoc), 2004-2005

Graduate Student, 1999-2004

New York University, Department of Chemistry, New York, NY

Advisor: Prof. Tamar Schlick

Website: monod.biomath.nyu.edu

Project 3: Macroscopic modeling, Brownian dynamics and Monte Carlo simulations, algorithm development

Developed a protein bead model for modeling flexible histone tails of nucleosome to enable computer simulations of chromatin fiber.

Mentored one Ph.D., one graduate student, and one undergraduate student in chromatin-related modeling projects.

Software:

A program to simulate chromatin with Brownian dynamics and Monte Carlo (contributed partially; FORTRAN).

Publications:

Arya, G.*, Zhang, Q.*, & Schlick, T., “Flexible histone tails in a new mesoscopic oligonucleosome model”, Biophysical Journal, 91: 133-150, 2006 (*contributed equally).

Zhang, Q., “Mesoscopic, microscopic, and macroscopic modeling of protein/DNA complexes”, Ph.D. Thesis, New York University, January 2005.

Project 2: Microscopic modeling, molecular dynamics simulation, free energy calculation

(collaborator: Prof. Suse Broyde, biologist, department of biology)

Interpreted the stereochemistry and position-dependent effects of carcinogen benzo[a]pyrene on transcription initiation-required TATA-TBP binding.

Software:

PCCMD – computing AMBER-compatible partial charges of carcinogen-modified B-deoxynucleotides in order to simulate cancer adducts (Perl; download here).

Publications:

Zhang, Q. & Schlick, T., “Stereochemistry and position-dependent effects of carcinogens on TATA/TBP binding”, Biophysical Journal, 90: 1865-1877, 2006.

Zhang, Q., Broyde, S., & Schlick, T., “Deformations of promoter DNA bound to carcinogens help interpret effects on TATA-element structure and activity”, Philosophical Transactions of The Royal Society of London Series A: Mathematical, Physical & Engineering Sciences (special volume on The Mechanics of DNA), 362: 1479-1496, 2004.

Project 1: Mesoscopic modeling, implicit-solvent electrostatics, algorithm development

Generalized the Discrete Surface Charge Optimization (DiSCO) algorithm, which simplifies electrostatic representations of macromolecules, by developing an irregular surface building method and the DiSCO software.

Applied DiSCO to supercoiled DNA-protein complexes and chromatin fibers.

Software:

DiSCO – building discrete surface charge models in order to increase efficiency of macromolecular electrostatics calculations (C, FORTRAN; go to the official download site).

ViewModel – visualizing DiSCO models (Matlab, C; download here).

Publications:

Zhang, Q., Beard, D. A., & Schlick, T., “Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DiSCO) algorithm”, Journal of  Computational Chemistry, 24: 2063-2074, 2003.

Sun, J., Zhang, Q., & Schlick, T., “Electrostatic mechanism of nucleosomal array folding revealed by computer simulation”, Proceedings of the National Academy of Sciences USA, 102: 8180-8185, 2005.

Huang, J., Zhang, Q., & Schlick, T., “Effect of DNA superhelicity and bound proteins on mechanistic aspects of the Hin-mediated and Fis-enhanced inversion”, Biophysical Journal, 85: 804-817, 2003.