Meng Cui

Research Associate Professor
  • Bouvé College of Health Sciences
  • Department of Pharmaceutical Sciences
  • Research Faculty
  • School of Pharmacy

Résumé/CV:
Office: ISEC 425
Phone: 617.373.5285
Email: m.cui@northeastern.edu

Education
– Heilongjiang University, PR China, B.S. (Organic Chemistry)
– Jilin University, PR China, Ph.D. (Physical Chemistry)

Specializations
– Structure and function of membrane proteins, such as GPCRs and Ion channels
– Ligand-protein, and protein-protein interactions
– Structure-based drug discovery

Research
My research focuses on understanding the relationship between structure and function of membrane proteins, such as G Protein-Coupled Receptors (GPCRs) and Ion channels. In this collaborative effort we utilize computational modeling techniques, molecular mutagenesis and functional expression of the receptors and channels to understand the signal-recognition and transduction mechanism of these important macromolecules. By means of computational and experimental approaches, we seek to understand how ligands or proteins interact and activate their targeting receptors or ion channels. Molecular Dynamics (MD) simulations based on all-atomic are being used to understand the ligand induced activation mechanism of ion channels. We are also developing computational approaches for loop modeling, flexible protein-ligand and protein-protein docking to achieve these goals.
In earlier work, we used Brownian Dynamics (BD) to successfully simulate the recognition between scorpion toxins and potassium channels. Our BD results indicate that the strong electrostatic interactions between scorpion toxins and potassium channels are the main driving force for their recognition and association. Our previous BD prediction of the interaction between scorpion toxin Lq2 and KcsA potassium channel was verified later by the potassium channel-charybdotoxin complex structure (PDB: 2A9H), which was determined by NMR studies. The consistency between the BD simulations and the experimental data indicates that our three-dimensional models of channel-toxin complexes are reasonable and can be used in further biological studies such as rational design of blocking agents of K(+) channels and mutagenesis in both toxins and K(+) channels. BD simulations can be used as a useful approach for understanding molecular recognition between proteins. We have improved Brownian Dynamics (BD) based approach for general protein docking studies, and further extended its applications on predicting dimerization of membrane proteins, such as GPCRs. We developed a local move Monte Carlo (LMMC) approach for loop predictions. These approaches are very useful tools for protein structure and function studies.
Obesity and diabetes have reached epidemic proportions worldwide. Previous studies showed that sweet taste receptor T1R2/T1R3, critical to sweet taste in the tongue, are also expressed in specialized taste cells of the gut where they sense glucose within the intestine. Characterization of sweet taste receptor and its activation and inhibition mechanism may lead to new therapies to treat diabetes, obesity, and gut disorders. We utilized computational modeling techniques, molecular mutagenesis and functional expression of the sweet taste-receptor to understand the signal-recognition and transduction mechanism of this important receptor. We had identified the possible binding-sites for sweeteners such as Aspartame, Neotame, Cyclamate, and sweet inhibitor lactisole. Our studies also provided new insights on the molecular mechanism of species-dependent sweet taste toward artificial sweeteners and sweet-tasting proteins. This work has important implications not only for the flavor industry, but also for diabetes treatments.
Molecular docking is a powerful approach for structure-based drug discovery. We applied molecular docking and dynamic receptor-based pharmacophore on therapeutic targets (Cyclophilin A and HIV-1 integrase) in treatment of HIV disease. In collaboration with our experimentalist colleagues, we studied ion channel structure and function by using Molecular Dynamics (MD) Simulations. The studies provided us new insights on the molecular mechanisms how PIP2, activators, inhbitors interact with potassium channels to modulate their activities. These ion channels are important therapeutic targets in treatment of heart, and Amyotrophic Lateral Sclerosis (ALS) diseases.

Selected Publications (posted July 2018)
1. M. Cui, X. Q. Huang, X. Luo, J. M. Briggs, R. Y. Ji, K. X. Chen, J. H. Shen, H. L. Jiang. Molecular Docking and 3D-QSAR Studies on Gag Peptide Analog Inhibitors Interacting with Human Cyclophilin A. J. Med. Chem. 2002, 21;45(24):5249-59
2. M. Cui, P. Jiang, E. Maillet, M. Max, R. Margolskee, R. Osman. The Heterodimeric Sweet Taste Receptor has Multiple Potential Ligand Binding Sites. Curr Pharm Des. 2006; 12(35): 4591-600.
3. B. Liu, M. Ha, X. Y. Meng, T. Kaur, M. Khaleduzzaman, Z. Zhang, P. Jiang, X. Li, M. Cui, Molecular Mechanism of Species-dependent Sweet Taste toward Artificial Sweeteners, Journal of Neuroscience, 2011 Jul 27;31(30):11070-6.
4. XY Meng, HX Zhang, M Mezei, M Cui. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011 Jun;7(2):146-57.
5. X. Y. Meng, H. X. Zhang, D. E. Logothetis, and M. Cui, The molecular mechanism by which PIP2 opens the intracellular G-loop gate of a Kir3.1 channel. Biophys J. 2012, May (102) 2049-2059.
6. M. Zhang, X.-Y. Meng, M. Cui, J. M. Pascal, D. E. Logothetis, J. F. Zhang. Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex. Nat Chem Biol. 2014 Sep;10(9):753-9.
7. W.S. Tobelaim, M. Dvir, G. Lebel, M. Cui, T. Buki, A. Peretz, M. Marom, Y. Haitin, D.E. Logothetis, J.A. Hirsch, B. Attali. Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5): E869-E878.
8. YW Nam, SN Baskoylu, D Gazgalis, R Orfali, M Cui, AC Hart, M Zhang. A V-to-F substitution in SK2 channels causes Ca2+ hypersensitivity and improves locomotion in a C. elegans ALS model. Sci Rep. 2018 Jul 16;8(1):10749.