Research |
Boxue TIAN, PhD

Boxue TIAN, PI

Dr. Boxue Tian is currently an assistant professor in the School of Pharmaceutical Sciences at Tsinghua University. He received his B.S. from East China University of Science and Technology in 2008, and M.S. from Orebro University (Sweden) in 2009. He received his PhD degree from National University of Ireland-Galway in 2012, where he worked with Prof. Leif A. Eriksson. He then conducted postdoctoral research from 2013 to 2020 at UCSF with Prof. Matthew P. Jacobson.

Research Interests

We are interested in computational chemistry and biology, including the development and applications of computational algorithms to important biological systems and pharmaceutical sciences.    
1)  Reaction Prediction:Combine QM and AI for predicting products of chemical reactions.    
2)  Drug Design: Design drugs with AI and computational chemistry.    
3)  Whole-Cell Model: Integrate multi-omics data to establish a virtual cell model for predicting interactions between xenobiotics and the cell.    

Scientific Contributions 

1. Computational approaches for the function prediction of terpene synthases    
Terpene synthases convert linear terpene substrates into fascinating cyclic natural products through complex carbocation rearrangements. Many products, such as taxol, are important intermediates or precursors of drugs. Predicting product specificity of terpene synthases is challenging because, among other reasons, a single mutation may alter product profiles, and no successful computational approach had been described previously.    
In collaboration with Prof. C. Dale Poulter, I developed an algorithm called iGen that automatically enumerates carbocation intermediates to predict the products of unknown terpene synthases (Figure 1). Application of this approach assisted the discovery of a novel terpene synthase (Proc. Natl. Acad. Sci. USA, 2015, 112, 5661-5666). This approach also allowed us to define the complete product chemical space of monoterponids (PLOS Comp. Bio. 2016, 12(8), e1005053).    

Figure 1. Example output of iGen, starting from one cyclized carbocation

    2. The chemical reaction calculator for organic chemistry and enzymatic reactions    
Using quantum chemistry to prospectively predict products and by-products of reactions is much more challenging than predicting mechanisms of forming known products. Building on our research on terpene synthases, I created a much more general “chemical reaction calculator” that works for most enzymes and chemical reactions (Figure 2). I validated this approach using 70 organic named reactions (web app available at, whereas previous papers had typically focused on one or a small handful of reactions. Named reactions are probably the most widely used set of reactions in organic synthesis. In addition to providing a diverse and challenging test set for our automated approach, these results may also be useful to help identify uncharacterized by-products in organic synthesis.    

Figure 2. Input and output of the chemical reaction calculator

Selected Publications

1. J. M. Bruining, Y. Wang, F. Oltrabella, B. Tian, H. Liu, P. Bhattacharya, S. Guo, J. M. Holton, R. J. Fletterick, M. P. Jacobson, P. M. England. Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite. Cell Chem Biol. 2019, 26, 1-12.    
    2. F. J. Cortez, P. Nguyen, C. Truillet, B. Tian, K. M. Kuchenbecker, M. J Evans, P. Webb, M. P Jacobson, R. J. Fletterick, P. M. England. Development of 5N-Bicalutamide, A High-affinity Reversible Covalent Antiandrogen. ACS Chem. Biol. 2017, 12, 2934-2939.    
    3. B. Tian, C. D. Poulter, M. P. Jacobson. Defining the Product Chemical Space of Monoterpenoid Synthases. PLOS Comp. Bio. 2016, 12(8), e1005053.    
    4. J. Y. Chow, B. Tian (Co-first author), G. Ramamoorthy, B. S. Hillerich, R. D. Seidel, S. C. Almo, M. P. Jacobson, C. D. Poulter. Computational-guided discovery and characterization of a sesquiterpene synthase from Streptomyces clavuligerus. Proc. Natl. Acad. Sci. USA, 2015, 112, 5661-5666.    
    5. G. Ramamoorthy, M. L. Pugh, B. Tian, R. M. Phan, L. B. Perez, M. P. Jacobson, C. D. Poulter. Synthesis and Enzymatic Studies of Bisubstrate Analogues for Farnesyl Diphosphate Synthase. J. Org. Chem. 2015, 80, 3902-3913.    
    6. B. Tian, F. H. Wallrapp, G. L. Holiday, J. Y. Chow, P. C. Babbitt, C. D. Poulter, M. P. Jacobson. Predicting the functions and specificity of triterpenoid synthases: A mechanism-based multi-intermediate docking approach. PLOS Comp. Bio. 2014, 10, e1003874.    
    7. S. Krishnan, R. M. Miller, B. Tian, R. D. Mullins, M. P. Jacobson, J. Taunton. Design of reversible, cysteine-targeted Michael acceptors guided by kinetic and computational analysis. J. Am. Chem. Soc. 2014, 136, 12624-12630.    
    8. M.P. Jacobson, C. Kalyanaraman, S. Zhao, B. Tian. Leveraging structure for enzyme function prediction: methods, opportunities, and challenges. Trends Biochem. Sci. 2014, 39, 363-371.    
    9. B. Tian, F. H. Wallrapp, C. Kalyanaraman, S. Zhao, L. A. Eriksson, M. P. Jacobson. Predicting Enzyme-Substrate Specificity with QM/MM Methods: A Case Study of the Stereo-specificity of D-glucarate Dehydratase. Biochemistry 2013, 52, 5511-5513.    
    10. B. Tian, N. An, W. P. Deng, L. A. Eriksson. Catalysts or Initiators?-Beckmann Rearrangement Revisited. J. Org. Chem. 2013, 78, 6782-6785.    
    11. N. An, B. Tian, L. A. Eriksson, W. P. Deng. Mechanistic Insight into Self-Propagation of Organo-Mediated Beckmann Rearrangement: A Combined Experimental and Computational Study. J. Org. Chem. 2013, 78, 4297-4302.    
    12. B. Tian, L. A. Eriksson. Catalytic Mechanism and Product Specificity of Oxidosqualene-Lanosterol Cyclase: A QM/MM Study. J. Phys. Chem. B 2012, 116, 13857-13862.    
    13. B. Tian, E. Erdtman, L. A. Eriksson. Catalytic Mechanism of Porphobilinogen Synthase: The Chemical Step Revisited by QM/MM Calculations. J. Phys. Chem. B 2012, 116, 12105-12112.    
    14.  B. Tian, L. A. Eriksson. Catalytic Mechanism and Roles of Arg197 and Thr183 in the Staphylococcus aureus Sortase A Enzyme. J. Phys. Chem. B 2011, 115, 13003-13011.    
    15. B. Tian, L. A. Eriksson. Structural changes of Listeria Monocytogenes Sortase A: A key to understanding the catalytic mechanism. Proteins: Struct., Funct., Bioinf. 2011, 79, 1564-1572.    
    16.  B. Tian, L. A. Eriksson. Catalytic Roles of Active Site Residues in 2-Methyl-3-hydroxypyridine-5-carboxylic Acid Oxygenase: An ONIOM/DFT Study. J. Phys. Chem. B 2011, 115, 1918-1926.    
    17. B. Tian, E. Eriksson, L. A. Eriksson. Can range-separated hybrid DFT functionals predict low-lying excitations? A Tookad case study. J. Chem. Theory Comput. 2010, 6, 2086-2094.    
    18. B. Tian, Y. Tu, Ǻ. Strid, L. A. Eriksson. Hydroxylation and Ring-opening Mechanism of an Unusual Flavoprotein Monooxygenase, 2-Methyl-3-hydroxypyridine-5-carboxylic Acid Oxygenase: A Theoretical Study. Chem. Eur. J. 2010, 16, 2557-2566.