Yong Zhang

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 with errors typically within 1-3% experimental ranges build a strong basis to provide critical missing information to help understand important experimental data, correct experimental errors, and guide future experiments with better desired properties/functions. The wide applicability of diversified computational methods from quantum mechanics, molecular mechanics, molecular dynamics, machine learning, and artificial intelligence together with the 24/7 availability of computational resources have been facilitating a broad range of scientific investigations to predict geometric, electronic, spectroscopic, mechanistic, material properties of systems from small molecules to large biomolecules, in gas, liquid, or solid phases. Such high quality computational research coupled with a comprehensive training protocol of scientific vision, scientific thinking, research skills, management skills, leadership skills, communication skills etc offer excellent opportunities for both undergraduate and graduate students to learn, practice, and achieve strong real-world problem solving skills.

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 132 published/accepted papers, 45 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 16.383), 11 in Angew. Chem. Int. Ed. (2^nd most cited chemical journal with IF of 16.823), 3 in Proc. Natl. Acad. Sci. U.S.A. (4^th most cited journal in multidisciplinary sciences with IF of 12.780), 1 in Nat. Chem. (IF of 24.274), 3 in ACS Catal. (IF of 13.700), and 1 in Chem. Sci. (IF of 9.969). The average journal IF of all papers published at US tenured/tenure-track positions is 9.681. 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 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.

3) Accurate drug binding structures and pro-drug activation mechanisms. Accurate structures of how drugs bind to their biomolecular targets pave an essential ground for structure-based drug discovery. However, due to the difficulty in obtaining x-ray structures of many drug-biomolecule complexes and the accuracy problem of conventional x-ray crystallography (to name a few examples: positional uncertainty of up to e.g. ~0.7 Å in bond length and ~90°in bond angle, structural uncertainty of messed identities of C/N/O atoms, and uncertainty of protonation states), there is a strong need to determine accurate drug binding structures. In addition, many drugs are pro-drugs, which need to be transformed to their active forms for pharmaceutical functions. Our group has provided accurate atomic level structures of some important bisphosphonate-protein complexes and their associate interaction modes, which help find new drug leads and understand the mechanistic origin of their drug activity and selectivity. Such drugs have a billion-dollar global pharmaceutical market and exhibit excellent activities in treating bone-resorption diseases, Paget’s disease, and cancer. Our group has previously also revealed the activation mechanism of the bestseller anticancer drug cisplatin. We are now exploring some new types of drugs to selectively inhibit some proteins of clinical interest and elucidating mechanisms of certain pro-drugs to treat cancers and blood diseases to help more people in the world.

Current Group Members

Graduate student:
Jia-Min Chu
Xinyi Zhao

Undergraduate student:
Dariya Baizhigitova
Daisy Morgan
Vrinda Modi

A total of 18 graduate and 37 undergraduate students have been trained for research in this group, including 64% from underrepresented groups (women and minorities).

After receiving the training in this lab at Stevens, all PhD students won some awards and many 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.

High quality undergraduate and graduate students with strong motivations are welcome to contact Professor Yong Zhang regarding the potential opportunity of joining his group's interesting and rewarding scientific endeavors.

Equipment:

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.

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

CH 322 Theoretical Chemistry
CH 421 Chemical Dynamics
CH 520 Advanced Physical Chemistry
CH 669 Applied Quantum Chemistry