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Integrative Structural and Computational Biology

Qinghai Zhang, PhD

Associate Professor
Department of Integrative Structural and Computational Biology
California Campus
Laboratory Website
(858) 784-7647

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

We are a multidisciplinary group working on chemical and structural biology of membrane proteins. Membrane proteins account for about one third of human genes and comprise more than 50% of human drug targets. Our laboratory develops novel methodologies and chemical tools enabling their structural and functional characterizations. A major interest is to study the interactions between membrane proteins and lipids that govern the protein stability and function. We are also interested in the development and discovery of small molecule therapeutics targeting membrane proteins of great biological and biomedical significance including transporters, GPCRs and channels. Towards this end, we have devoted efforts to solve membrane protein structures for drug binding and mechanistic studies. Developing synthetic methodologies to make biologically relevant molecules is another component of our laboratory.


Ph.D., Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 2001

Selected References

Ishchenko A, Peng L, Zinovev E, Vlasov A, Lee SC, Kuklin A, Mishin A, Borshchevskiy V, Zhang Q, Cherezov V. Chemically Stable Lipids for Membrane Protein Crystallization. Cryst. Growth and Des. 2017, 17:3502-3511.

Padayatti PS, Leung JH, Mahinthichaichan P, Tajkhorshid E, Ishchenko A, Cherezov V, Soltis SM, Jackson JB, Stout CD, Gennis RB, and Zhang Q. Critical Role of Water Molecules in Proton Translocation by the Membrane-bound Transhydrogenase. Structure 2017, 25:1111-9.

Shah MB, Liu J, Zhang Q, Stout CD and Halpert JR. Halogen-p Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity. ACS Chem. Biol. 2017, 12:1204-1210.

Bennett BC, Purdy MD, Baker KA, Achara C, McIntire WE, Stevens RC, Zhang Q, Harris A, Abagyan R, Yeager M. An Electrostatic Mechanism for Ca2+-mediated Regulation of Gap Junction Channels. Nat. Commun. 2016, 7:8770.

Shah MB, Huo L, Liu J, Zhang Q, Dearing MD, Wilderman PR, Szklarz G, Stout CD, Halpert JR. Structure-Function Analysis of Mammalian CYP2B Enzymes using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism. Mol. Pharmacol. 2016, 89:435-45.

Szewczyk P,  Tao H, McGrath AP, Villaluz M,  Rees SD, Lee SC, Doshi R, Urbatsch IL, Zhang Q, Chang G. Structural Snapshots of Ligand Entry, Malleable Binding, and Induced Helical Movement in P-glycoprotein. Acta Crystallogr. D Biol. Crystallogr. 2015, 71:732-41.

Moeller A, Lee SC, Tao H, Speir J, Chang G, Urbatsch IL, Potter CS, Carragher B, Zhang Q. Distinct Conformational Spectrum of Homologous Multidrug ABC Transporters. Structure 2015, 23:450-60.

Shah MB, Wilderman PR, Liu J, Jang H-H, Zhang Q, Stout CD, Halpert JR. Structural and Biophysical Characterization of Human Cytochromes P450 2B6 and 2A6 Bound to Volatile Hydrocarbons: Analysis and Comparison. Mol Pharmacol. 2015, 87:649-59.

Peng L, Mo F, Zhang Q. Cholate-based Synthesis of Size-tunable Cage Compounds. J. Org. Chem. 2015, 80:1221-8.

Wang A, Stout CD, Zhang Q, Johnson EF. Contributions of Ionic Interactions and Protein Dynamics to Cytochrome P450 2D6 (CYP2D6) Substrate and Inhibitor Binding. J. Biol. Chem. 2015, 290:5092-14.

Hildebrandt E, Zhang Q, Cant N, Ding H, Dai Q, Peng L, Fu Y, Delucas LJ, Ford R, Kappes JC, Urbatsch IL. A Survey of Detergents for the Purification of Stable, Active Human Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). BBA – Biomembranes. 2014, 1838:2825-37.

Martinez L, Arnaud O, Henin E, Tao H, Chaptal V, Doshi R, Andrieu T, Dussurgey S, Tod M, Di Pietro A, Zhang Q, Chang G, Falson P. Understanding Polyspecificity within the Substrate-binding Cavity of the Human Multidrug Resistance P-glycoprotein. FEBS J. 2014, 281:673-82.

Tao H, Peng L, Zhang Q. Synthesis of Azole-Enriched Cyclopeptides by A Purification Free, Solid Phase-Based Cyclitive Cleavage Strategy. ACS Comb. Sci. 2013, 15:447-51.

Shah MB, Kufareva I, Pascual J, Zhang Q, Stout CD, Halpert JR. A Structural Snapshot of Cytochrome P450 2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States. J. Pharmacol. Exp. Ther. 2013, 346:113-20.

Tao H, Lee SC, Moeller A, Roy RS, Siu FY, Zimmermann J, Stevens RC, Potter CS, Carragher B, Zhang Q. Engineered Nanostructured b-Sheet Peptides Protect Membrane Proteins. Nat. Methods 2013, 10:759-61.

Marcoux J, Wang S, Politis A, Reading E, Ma J, Biggin P, Zhou M, Tao H, Zhang Q, Chang G, Morgner N, Robinson CV. Mass Spectrometry Reveals Synergistic Effects of Nucleotides, Lipids and Drugs Binding to A Multidrug Resistance Efflux Pump. Proc. Natl. Acad. Sci. USA 2013, 110:9704-9.

Lee SC, Bennett BC, Hong W-X, Fu Y, Baker KA, Marcoux J, Robinson CV, Ward AB, Halpert JR, Stevens RC, Stout CD, Yeager Y, Zhang Q. Steroid-Based Facial Amphiphiles for Stabilization and Crystallization of Membrane Proteins. Proc. Natl. Acad. Sci. USA 2013, 110:E12-3-11.