High Accuracy Computational Chemistry to Help Solve Experimental Problems
Our research focuses on developing and utilizing computational methods to provide accurate information for various kinds of molecular and biomolecular systems, particularly those of broad impact on biomedicine and sustainable chemistry.
The high accuracy computational results build a solid basis to provide critical missing information to not only help understand important experimental data, but also enable corrections of experimental errors and facilitate new experimental studies.
Our prior research has enabled 1) accurate predictions of ~20 widely used spectroscopic properties with theory-versus-experiment correlation coefficient R2 around 0.99; 2) accurate structure refinement and determination for active sites of ~20 metalloproteins; 3) unprecedented mechanistic details for >20 important therapeutic agents, proteins of clinical interest, and green catalysts/biocatalysts.
Among a total of 130 published/accepted papers, 44 are in the following high-profile journals with impact factor (IF) >~10: 26 in J. Am. Chem. Soc. (most cited chemical journal with IF of 15.419), 10 in Angew. Chem. Int. Ed. (2nd most cited chemical journal with IF of 15.336), 3 in Proc. Natl. Acad. Sci. U.S.A. (4th most cited journal in multidisciplinary sciences with IF of 11.205), 1 in Nat. Chem. (IF of 24.427), 3 in ACS Catal. (IF of 13.084), and 1 in Chem. Sci. (IF of 9.825). The average journal IF of all papers published at US tenured/tenure-track positions is 9.006. The complete list of the publications can be seen via this URL: https://scholar.google.com/citations?user=hDumUHUAAAAJ&hl=en
Our current research interests are mainly in the following two areas:
1) metalloprotein/metal mediated binding, formation, conversion, and detection of biological HNO and NO. These small molecules play vital roles in the cellular survival and signaling/regulation activities. Studies of NO’s effects in biomedicine have been awarded Nobel Prize. HNO, as a sibling molecule of NO, also plays unique roles in many biological processes, such as vascular relaxation, enzyme activity regulation, and neurological function regulation. It was found to be more favorable than NO to treat medical problems such as heart failure, and has potential applications in treating alcoholism, cancer, and other diseases. But many structural and mechanistic details of these important functional processes are still unknown. Our group has been continuously providing some previously unknown critical structural and mechanistic information in this area, such as the first atomic level HNO bound protein active site structure, first heme and non-heme protein mediated HNO to NO conversion mechanistic pathway details, and first metal-based selective HNO sensor's reactivity mechanism, and first non-native one-electron reduction reactivity mechanism for NO in models of nitric oxide reductases. We are now expanding our research to more of such systems and reactions to provide novel mechanistic ideas for sensor optimization, drug activity improvement, and signal transduction rewiring to help advance relevant biomedical research.
2) Bioengineered catalysts with artificial functions for sustainable chemistry. To make our earth sustainable is very important to everyone and our future generations. In order to help reach this grand goal, one fundamental topic in sustainable chemistry is to develop excellent catalysts that can utilize inexpensive earth-abundant and environmentally benign elements (no toxicity) to perform highly reactive and selective atom-economic chemical transformations for manufacturing various desired materials, drugs, and other useful substances, at room temperature and ambient pressure (no additional cost for high or low temperature/pressure management), in aqueous solution (no toxic organic solvents). Nature has many beautiful examples and engineering native enzymes with new artificial functions for numerous important non-native chemical transformations has shown highly promising reactivity and selectivity results for sustainable chemistry. Novel heme protein based biocatalysts exhibit excellent catalytic performance for a wide range of chemical reactions, including but not limited to cyclopropanation, C-H functionalization, Si-H insertion, N-H insertion, S-H insertion, B-H insertion, aldehyde olefination, sigmatropic rearrangement, cyclopropenation, bicyclobutanation. A recent Nobel Prize was awarded to a few experimental pioneers in this field. Our group has provided some first computational mechanistic insights into the electronic structures of heme carbenes and the origins of their reactivity, stereoselectivity, and chemoselectivity results in various heme carbene transfer reactions (such as cyclopropanation, C-H insertion, and Si-H insertion), which have facilitated many experimental studies. We are now expanding our research to more bioengineered catalysts and more non-native reactions to further advance this field toward a more sustainable life for our world.
Current Group Members
A total of 17 graduate and 32 undergraduate students have been trained for research in this group, including ~60% from underrepresented groups (women and minorities).
After joining this lab at Stevens, all PhD students won some awards and most undergraduate students won up to 7 awards and scholarships, including national level honors such as ACS Division of Physical Chemistry Undergraduate Award, ACS Division of Inorganic Chemistry Undergraduate Award, and one of only 25 Physical Chemistry students nationwide selected to present at ACS national meetings.
Many students have publications in prestigious or even top journals, including undergraduate students.
For those who went to graduate and medical schools, each receives up to 7 offers from prominent universities such as Yale, John Hopkins, Cornell/Rochefeller/MSK, UCLA, University of Michigan, New York University, Rutgers.
In addition, a number of students become scientists and professors in academia or industry after graduation from this lab.
This lab has a computational cluster in the university's Data Center with 436 cores, 1014 GB RAM, and 7.2 TB hard drive, with additional access to a school computational cluster of 880 cores, 4160 GB RAM, and 240 TB hard drive. Each student has a high-performance PC.
- CCB Research and Infrastructure Committee Member
- CCB Undergraduate Education Committee Member
- CCB Promotion and Tenure Committee Chair
- School of Engineering and Science Advanced Computing Advisory Group Member
- School of Engineering and Science Honors and Awards Committee Member
- School of Engineering and Science Research Committee Member
- Academic Planning and Resources Committee Member
- CCB Graduate Admission Committee Member
2019-present Professor, Stevens Institute of Technology
2010-2019 Associate Professor, Stevens Institute of Technology (tenured in 2015)
2007-2010 Assistant Professor, University of Southern Mississippi
2005-2007 Research Scientist, University of Illinois Urbana-Champaign
2000-2005 Postdoctoral Research Associate, University of Illinois Urbana-Champaign
1999-2000 Associate Professor, Nanjing University
- American Chemical Society Member
- American Association for the Advancement of Science Member
- Society of Biological Inorganic Chemistry Member
- Society of Porphyrins and Phthalocyanines Member
- Tian, S.; Fan, R.; Albert, T.; Khade, R. L.; Dai, H.; Harnden, K. A.; Hosseinzadeh, P.; Liu, J.; Nilges, M. J.; Zhang, Y.; Moënne-Loccoz, P.; Guo, Y.; Lu, Y. (2021). Stepwise nitrosylation of the nonheme iron site in an engineered azurin and a molecular basis for nitric oxide signaling mediated by nonheme iron proteins. Chemical Science (19 ed., vol. 12, pp. 6569-6579).
- Vargas, D. A.; Khade, R. L.; Zhang, Y.; Fasan, R. (2019). Biocatalytic Strategy for Highly Diastereo- and Enantioselective Synthesis of 2,3-Dihydrobenzofuran-Based Tricyclic Scaffolds. Angewandte Chemie - International Edition (30 ed., vol. 58, pp. 10148-10152).
- Tinoco, A.; Wei, Y.; Bacik, J. P.; Carminati, D. M.; Moore, E. J.; Ando, N.; Zhang, Y.; Fasan, R. (2019). Origin of High Stereocontrol in Olefin Cyclopropanation Catalyzed by an Engineered Carbene Transferase. ACS Catalysis (2 ed., vol. 9, pp. 1514-1524).
- Selvan, D.; Prasad, P.; Farquhar, E. R.; Shi, Y.; Crane, S.; Zhang, Y.; Chakraborty, S. (2019). Redesign of a Copper Storage Protein into an Artificial Hydrogenase. ACS Catalysis (pp. 5847-5859).
- Abucayon, E. G.; Khade, R. L.; Powell, D. R.; Zhang, Y.; Richter-Addo, G. B. (2019). Not Limited to Iron: A Cobalt Heme--NO Model Facilitates N--N Coupling with External NO in the Presence of a Lewis Acid to Generate N2O. Angewandte Chemie International Edition (51 ed., vol. 58, pp. 18598--18603). German Chemical Society.
- Shi, Y.; Zhang, Y. (2018). Mechanisms of HNO Reactions with Ferric Heme Proteins. Angewandte Chemie - International Edition (51 ed., vol. 57, pp. 16654-16658).
- Malwal, S. R.; O'Dowd, B.; Feng, X.; Turhanen, P.; Shin, C.; Yao, J.; Kim, B. K.; Baig, N.; Zhou, T.; Bansal, S.; Khade, R. L.; Zhang, Y.; Oldfield, E. (2018). Bisphosphonate-Generated ATP-Analogs Inhibit Cell Signaling Pathways. Journal of the American Chemical Society (24 ed., vol. 140, pp. 7568-7578).
- Bhagi-Damodaran, A.; Reed, J. H.; Zhu, Q.; Shi, Y.; Hosseinzadeh, P.; Sandoval, B. A.; Harnden, K. A.; Wang, S.; Sponholtz, M. R.; Mirts, E. N.; Dwaraknath, S.; Zhang, Y.; Moënne-Loccoz, P.; Lu, Y. (2018). Heme redox potentials hold the key to reactivity differences between nitric oxide reductase and heme-copper oxidase. Proceedings of the National Academy of Sciences of the United States of America (24 ed., vol. 115, pp. 6195-6200).
- Malwal, S. R.; Gao, J.; Hu, X.; Yang, Y.; Liu, W.; Huang, J. W.; Ko, T. P.; Li, L.; Chen, C. C.; O'Dowd, B.; Khade, R. L.; Zhang, Y.; Zhang, Y.; Oldfield, E.; Guo, R. T. (2018). Catalytic Role of Conserved Asparagine, Glutamine, Serine, and Tyrosine Residues in Isoprenoid Biosynthesis Enzymes. ACS Catalysis (5 ed., vol. 8, pp. 4299-4312).
- Abucayon, E. G.; Khade, R. L.; Powell, D. R.; Zhang, Y.; Richter-Addo, G. B. (2018). Lewis Acid Activation of the Ferrous Heme-NO Fragment toward the N-N Coupling Reaction with NO to Generate N2O. Journal of the American Chemical Society (12 ed., vol. 140, pp. 4204-4207).
- Wei, Y.; Tinoco, A.; Steck, V.; Fasan, R.; Zhang, Y. (2018). Cyclopropanations via Heme Carbenes: Basic Mechanism and Effects of Carbene Substituent, Protein Axial Ligand, and Porphyrin Substitution. Journal of the American Chemical Society (5 ed., vol. 140, pp. 1649-1662).
- Reed, J. H.; Shi, Y.; Zhu, Q.; Chakraborty, S.; Mirts, E. N.; Petrik, I. D.; Bhagi-Damodaran, A.; Ross, M.; Moënne-Loccoz, P.; Zhang, Y.; Lu, Y. (2017). Manganese and Cobalt in the Nonheme-Metal-Binding Site of a Biosynthetic Model of Heme-Copper Oxidase Superfamily Confer Oxidase Activity through Redox-Inactive Mechanism. Journal of the American Chemical Society (35 ed., vol. 139, pp. 12209-12218).
- Bhagi-Damodaran, A.; Kahle, M.; Shi, Y.; Zhang, Y.; Ädelroth, P.; Lu, Y. (2017). Insights Into How Heme Reduction Potentials Modulate Enzymatic Activities of a Myoglobin-based Functional Oxidase. Angewandte Chemie - International Edition (23 ed., vol. 56, pp. 6622-6626).
- Bhagi-Damodaran, A.; Michael, M. A.; Zhu, Q.; Reed, J.; Sandoval, B. A.; Mirts, E. N.; Chakraborty, S.; Moënne-Loccoz, P.; Zhang, Y.; Lu, Y. (2017). Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases. Nature Chemistry (3 ed., vol. 9, pp. 257-263).
CH 322 Theoretical Chemistry
CH 421 Chemical Dynamics
CH 520 Advanced Physical Chemistry
CH 669 Applied Quantum Chemistry