Department of Chemistry

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Sunil Saxena

Professor and Department Chair

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711 CHVRN
Chevron Science Center, 219 Parkman Avenue

Pittsburgh, PA 15260
412-624-8680

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Research Overview

 

Analytical, Biophysical, and Physical Chemistry

We develop pulsed electron spin resonance methods and apply them to otherwise inaccessible problems in biophysics and materials sciences. The coupling of electron spin angular momentum to its environment—as revealed by the ESR spectrum—provides rich information about the electronic, structural and dynamical properties of the molecule. We develop ESR methodology that can measure distances (typically over 1‐9 nm) in spin labeled complexes. In recent years we have also developed site-directed Cu(II) labeling of proteins and nucleic acids. In proteins our methodology provides a straightforward method to elucidate biophysical information that is inaccessible to commonly used ESR labels. Examples include the direct measurement of protein backbone dynamics at β-sheet sites, and rigid Cu(II)-Cu(II) distance measurements that enable high precision in the analysis of protein structure, conformational changes, and interactions with other biomolecules. Likewise, in DNA, we have discovered a new nucleotide-independent, site-specific Cu(II) spin label that resides within the interior of the DNA helix. Cu(II) -based distance measurements directly measure the most-probable backbone distance. Additionally, we develop models for the interpretation of the ESR distance information, primarily utilizing molecular dynamics (MD) simulations. Ongoing projects in the group seek to shed light on how biomolecular dynamics and protein-DNA interactions lead to function in a metalloregulator and an endonuclease.

The students in the group are trained in the interdisciplinary interface between Chemistry and Biophysics gaining skills that range from cutting-edge spectroscopy and molecular modeling to protein mutagenesis and expression. The students are continuously challenged to gain new skills to prepare them for an everchanging professional environment. Roughly half of the alumni are in academia while the other half are in pharmaceutical industry.

Our science is highly collaborative, and we value the ability to work as a team. We emphasize the holistic training of a diverse group of students and focus on the development of both hard and soft professional skills. We invite you to visit our group website and to contact us to explore the diversity of research projects currently underway in our group.

 

Awards

  • Crano Memorial Lecture, ACS-Akron Section, 2014
  • Arts and Sciences Tina and David Bellet Teaching Excellence Award, 2012
  • NSF CAREER Award, 2004-2009

CV

Publications

“Cu(II)-based DNA labeling identifies the structural link between transcriptional activation and termination in a metalloregulator,” J. Casto, A. Mandato, L. Hofmann, I. Yakobov, S. Ghosh, S. Ruthstein and S. Saxena Chem. Sci 2022, 13, 1693
“Structures of highly flexible intracellular domain of human alpha7 nicotinic acetlycholine receptor,” V Bondarenko, M. M. Wells, Q. Chen, T. S. Tillman, K. Singewald, M. J. Lawless, J. Caporoso, N. Brandon, , S. Saxena, E. Lindahl, Y. Xu, P. Tang Nat. Comm. 2022, 13, 793
“Nanoscale spin detection of CuCl2 molecules using double-electron resonance at room temperature,” K. Zhang, S. Ghosh, S. Saxena, G. Dutt Phys. Rev. B 2021, 104, 224412
“Going the dHis-tance: Site-directed Cu(II) labeling of proteins and nucleic acids,” A. Gamble Jarvi, X. Bogetti, K. Singewald, S. Ghosh, S. Saxena Acc. Chem. Res 2021, 51 6, 1481
“Benchmark test and guidelines for DEER/PELDOR experiments on nitroxide-labeled biomolecules,”  O. Schiemann, C. A. Heubach, D. Abdullin, K. Ackermann, M. Azarkh, E. Bagryanskaya, M. Drescher, B. Endeward, J. H. Freed, L. Galazzo, D. Goldfarb, T. Hett, L. E. Hofer, L. F. Ibanez, E. J. Hustedt, S. Kucher, I. Kuprov, J. E. Lovett, A. Meyer, S. Ruthstein, S. Saxena, S. Stoll, C. Timmel, M. D. Valentin, H. S. Mchaourab, T. F. Prisner, B. E. Bode, E. Bordignon, M. Bennati, G. Jeschke. J. Am. Chem. Soc 2021, 17875
“Cleavage-resistant Protein Labeling with Hydrophilic Trityl Enables Distance Measurements In-Cells,” Z. Hasanbasri, K. Singewald, T. Gluth, B. Driesschaert, S. Saxena J. Phys. Chem. B 2021, 125, 5265
“Buffer effects on Site Directed Cu(II) labeling using the double Histidine motif,” A. Gamble Jarvi, J. Casto, S. Saxena J. Magn. Reson 2020, 320, 106848
“Double-Histidine based EPR measurements at room temperature permit site-specific elucidation of hidden dynamics in enzymes,” K. Singewald, X. Bogetti, K. Sinha, G. R. Rule, S. Saxena Angew. Chem. Int. Ed 2020, 51, 59
“Cu(II)-based distance measurements by pulsed EPR provide distance constraints for DNA backbone conformations in solution,” S. Ghosh, M. J. Lawless, H. Brubaker, K. Singewald, M. Kurpiewski, L. Jen-Jacobson, S. Saxena Nucleic Acids Res 2020, 48, e49
“Structural and dynamic origins of ESR lineshapes in spin-labeled proteins: the insights from spin dynamics simulations based on long MD trajectories,” S.A. Izmailov, S. O. Rabdano, Z. Hasanbasri,  I. S. Podkorytov, S. Saxena, Nikolai R. Skrynnikov Sci. Rep 2020, 10, 957
“19F paramagnetic relaxation based NMR for quaternary structural restraints of ion channels,” V. Bondarenko, M.M Wells, Q. Chen, K.C. Singewald, S. Saxena, Y. Xu, P. Tang ACS Chem. Bio 2019, 14 10, 2160-2165
“Designing open metal sites in metal-organic frameworks for paraffin/olefin separations,” M.H. Mohamed, Y. Yang, L. Li, S. Zhang, J.P. Ruffley, A Gamble Jarvi, S. Saxena, G. Veser, K. J. Johnson, N. Rosi, J. Am. Chem. Soc 2019, 141 13003
“Understanding and controlling the metal-directed assembly of terpyridine-functionalized coiled-coil peptides,” K. A. Scheib, N. A. Tavenor, M. J. Lawless, S. Saxena, W. S. Horne Chem Comm. 2019, 55 7752
“The effect of MnO2 of different structures on activation of peroxymonosulphate for bisphenol A degradation under acidic conditions,” J. Huang, Y. Dai, K. Singewald, C.-C. Liu, S. Saxena, H. Zhang Chem Eng. J. 2019, 370, 906
“EPR spectroscopy detects various active state conformations of the transcriptional regulator CueR,” H. Sameach, S. Ghosh, L. Gevorkyan-Airapetov, S. Saxena, S. Ruthstein Angew. Chem. Intl. Ed. 2019, 58, 3053
“Efficient localization of a metal ion within a protein by Cu(II)-based EPR distance measurements,” A. Gamble Jarvi, T. F. Cunningham, S. Saxena Phys. Chem. Chem. Phys. 2019, 21, 10238