Zhijun Li PhD
Zhijun Li PhD
Associate Professor of Bioinformatics
Research Assistant Professor of Cell Biology and Biotechnology
BS (Tsinghua University)
MS (Tsinghua University)
PhD (Vanderbilt University)
Using computational and bioinformatic methods to generate and analyze three-dimensional structures of protein molecules, and to gain insight into protein sequence, structure, and function relationships.
My current research efforts focus on utilizing computational and bioinformatics methods to gain insight into protein sequence, structure and function relationships and to explore their application in molecular modeling, drug design and protein engineering.
There are several research areas I'm interested in. First is the development of computational tools to aid in the structural prediction of transmembrane proteins such as G-protein coupled receptors. Transmembrane proteins are essential to many important cellular activities such as signal and energy transduction, mediation of the senses and immune recognition. These proteins are important therapeutic targets. The G-protein coupled receptor (GPCR) superfamily alone represents the targets of ~27% of drugs currently available in the market. Despite their biological importance, high-resolution TM protein structures remain scarce compared with soluble proteins. As a result, computational modeling has played a key role in the studies of membrane proteins.
A second research area of interest is to apply structural modeling tools to the construction of protein and protein-complex models designed to help elucidate biological mechanisms. An active project currently ongoing in this area is to model three-dimensional structures of chemoreceptor-CheR complexes through collaboration with experimentalists. Another project is to construct the structure models of tumor endothelial marker-antibody complex.
The third area of interest is to apply the knowledge gained through the analysis of protein structures to biomedical problems such as computer-aided molecular design and protein engineering. We're especially interested in the emerging field of network medicine. For instance, works are under-way to design selective protein kinase inhibitors for the treatment of cancer.
Selected Scholarly Activity
I. Kufareva, V. Katritch, participants of GPCR Dock 2013 (Box 1), R. C. Stevens, and R. Abagyan, Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges. Structure (2014) 22: 1120-1139.
S. Chaudhuri, S. Pratap, V. Paromov, Z. Li, and H. Xie. Identification of a diguanylate cyclase and its role in porphyromonas gingivalis virulence. Infection and Immunity (2014) 82(7): 2728-2735.
A. J. Heim and Z. Li, Developing a high-quality scoring function for membrane protein structures based on specific inter-residue interactions. J. Computer-Aided Molecular Design (2012) 26: 301-309.
J. Gao, Z. Li, T. Russelld, and Z. Li, Antibody affinity purification using metallic nickel particles. J. Chromatography B, (2012) 895–896: 89–93.
V. Pabuwal and Z. Li, Comparison analysis of primary ligand binding sites in seven-helix membrane proteins. Biopolymers (2011) 95: 31-38.
J. Gao and Z. Li, Uncover the conserved property underlying sequence-distant and structure-similar proteins. Biopolymers (2010) 93: 340-347.
J. Gao and Z. Li, Conserved network properties of helical membrane protein structures and its implication for improving membrane protein homology modeling at the twilight zone. J. Computer-Aided Mol. Des. (2009) 23: 755-763.
U. K. Muppirala, S. Desensi, T. P. Lybrand, G. L. Hazelbauer and Z. Li, Molecular modeling of flexible arm-mediated interactions between a bacterial chemoreceptor and its modification enzyme. Protein Sci. (2009) 18: 1702-1714.
J. Gao and Z. Li, Comparing four different approaches for the determination of inter-residue interactions provides insight for the structure prediction of helical membrane proteins. Biopolymers (2009) 91: 547-556.
V. Pabuwal and Z. Li, Comparative analysis of the packing topology of structurally important residues in helical membrane and soluble proteins. Protein Eng. Des. Sel. (2009) 22: 67-73.
J. Gao and Z. Li, Inter-residue interactions in protein structures exhibit power-law behavior Biopolymers (2008) 89: 1174-1178.
J. F. Galan, J. Gao, V. Pabuwal, P. J. Meek and Z. Li, Application of network theory in understanding and predicting protein structure and function. Current Proteomics (2008) 5(3): 181-190.
W. Lai, L. Huang, P. Ho, Z. Li, D. Montefiori and C.-H. Chen, Small molecules target HIV-1 V3 loop with broad anti-HIV-1 entry activity. Antimicrob. Agents Chemother. (2008) 52: 128-136.
V. Pabuwal and Z. Li, Network pattern of residue packing in helical membrane proteins and its application in membrane protein structure prediction. Protein Eng. Des. Sel. (2008) 21: 55-64.
U. K. Muppirala and Z. Li, A simple approach for protein structure discrimination based on the network pattern of conserved hydrophobic residues. Protein Eng. Des. Sel. (2006) 19: 265-275.
M. Dong, Z. Li, D. I. Pinon, T. P. Lybrand, and L. J. Miller, Spatial approximation between the amino terminus of a peptide agonist and the top of the sixth transmembrane segment of the secretin receptor. J. Bio. Chem. (2004) 279: 2894-2903.
M. Dong*, Z. Li*, M. Zang, D. I. Pinon, T. P. Lybrand and L. J. Miller, Spatial approximation between two residues in the mid-region of secretin and the amino terminus of its receptor. Incorporation of seven sets of such constraints into a three-dimensional model of the agonist-bound secretin receptor. J. Bio. Chem. (2003) 278: 48300-48312. *Contributed equally
M. Zang, M. Dong, D. I. Pinon, X.-Q. Ding, E. M. Hadac, Z. Li, T. P. Lybrand, and L. J. Miller, Spatial approximation between a photolabile residue in position 13 of secretin and the amino- terminus of the secretin receptor, Mol. Pharmacology (2003) 63: 993-1001.
M. Dong, M. Zang, D. I. Pinon, Z. Li, T. P. Lybrand, and L. J. Miller, Interaction among four residues distributed through the secretin pharmacophore and a focused region of the secretin receptor amino terminus, Mol. Endocrinology (2002) 16: 2490-2501.
Z. Li, L. Huang, P. Dande, B. Gold, and M. P. Stone, Structure of a tethered cationic 3-aminopropyl chain incorporated into an oligodeoxynucleotide: Evidence for 3 '-orientation in the major groove accompanied by DNA bending. J. Am. Chem. Soc. (2002) 124: 8553-8560.
Z. Li, P. J. Tamura, A. S. Wilkinson, C. M. Harris, T. M. Harris, and M. P. Stone, Intercalation of the (1R,2S,3R,4S)-N-6-[1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz[a]anthracenyl)]-2 '-deoxyadenosyl adduct in the N-ras codon 61 sequence: DNA sequence effects. Biochemistry (2001) 40: 6743-6755.
Z. Li, H.-Y. Kim, P. J. Tamura, C. M. Harris, T. M. Harris, and M. P. Stone, Intercalation of the (1S,2R,3S,4R)-N-6[1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz[alpha]anthracenyl)]-2 '-deoxyadenosyl adduct in an oligodeoxynucleotide containing the human N-ras codon 61 sequence. Biochemistry (1999) 38: 16045-16057.
Z. Li, H.-Y. Kim, P. J. Tamura, C. M. Harris, T. M. Harris, and M. P. Stone, Role of a polycyclic aromatic hydrocarbon bay region ring in modulating DNA adduct structure: The non-bay region (8S,9R,10S,11R)-N-6-[11-(8,9,10,11-tetrahydro-8,9,10-trihydroxybenz[a] anthracenyl)]-2 '-deoxyadenosyl adduct in codon 61 of the human N-ras protooncogene. Biochemistry (1999) 38: 14820-14832.
Z. Li, H. Mao, H.-Y. Kim, P. J. Tamura, C. M. Harris, T. M. Harris, and M. P. Stone, Intercalation of the (-)-(1R,2S,3R,4S)-N-6-[1-benz[a]anthracenyl]-2 '-deoxyadenosyl adduct in an oligodeoxynucleotide containing the human N-ras codon 61 sequence. Biochemistry (1999) 38: 2969-2981.
S. Xu and Z. Li, Alignment mechanism of liquid crystal molecules on the fluorated polyimide surface. Tsinghua Science and Technology (1997) 2: 798-800.
(Chinese) S. Xu and Z. Li, Study of alignment process technologies of liquid crystal molecules on surface of fluorated polyimide. Journal of Tsinghua University (Science and Technology) (1997) 37: 17-20.
|Office location:||McNeil Science and Technology Center Room 219|
|Mailing address:||Box 100|
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
z [dot] li [at] usciences [dot] edu