Department of Chemistry, Carnegie Mellon University
PhD, Theoretical Chemistry, Jackson State University

The Isayev lab works at the interface of theoretical chemistry, pharmaceutical sciences and computer science. In particular, we are using molecular simulations and artificial intelligence (AI) to solve hard problems in chemistry. We are working towards the acceleration of molecular discovery by the combination of AI, informatics and high-throughput quantum chemistry. We also focus on both generative and predictive ML models for chemical and biological data. Details on specific projects can be found below.

Accelerating computational chemistry with deep learning: We are developing fully transferable deep learning potentials for molecular and materials systems. Such atomistic potentials are highly accurate compared to reference QM calculations at speeds 107faster. Neural network potentials are shown to accurately represent the underlying physical chemistry of molecules through various test cases including chemical reactions, kinetics, thermochemistry, structural optimization, and molecular dynamics simulations.

Materials informatics: Material informatics is a rapidly emerging data- and knowledge-driven approach for the identification of novel materials for a range of applications, including solar energy conversion. As the proliferation of high-throughput methods in chemical sciences is increasing the wealth of data in the field, the gap between accumulated-information and derived knowledge widens. We address the issue of scientific discovery in chemical and biological databases by introducing novel analytical approaches based on large-scale data mining and machine learning.

De Novo molecular design: The de novo molecular design problem involves generating novel molecular structures or focused molecular libraries with desirable properties. It solves a so-called inverse design problem. We develop artificial intelligence method that enables the design of chemical libraries with the desired physicochemical and biological properties or both.

Most Cited Publications
  1. "Machine learning for molecular and materials science," Keith T Butler, Daniel W Davies, Hugh Cartwright, Olexandr Isayev, Aron Walsh. Nature, 559, 547-555 (2018)
  2. "ANI-1: an extensible neural network potential with DFT accuracy at force field computational cost," Justin S Smith, Olexandr Isayev, Adrian E Roitberg. Chemical science, 8, 3192-3203 (2017)
  3. "Universal fragment descriptors for predicting properties of inorganic crystals," Olexandr Isayev, Corey Oses, Cormac Toher, Eric Gossett, Stefano Curtarolo, Alexander Tropsha. Nature communications, 8, 1-12 (2017)
  4. "Materials cartography: representing and mining materials space using structural and electronic fingerprints," Olexandr Isayev, Denis Fourches, Eugene N Muratov, Corey Oses, Kevin Rasch, Alexander Tropsha, Stefano Curtarolo. Chemistry of Materials, 27, 735-743 (2015)
  5. "Deep reinforcement learning for de novo drug design," Mariya Popova, Olexandr Isayev, Alexander Tropsha. Science advances, 4, eaap7885 (2018)
Recent Publications
  1. "Crowdsourced mapping of unexplored target space of kinase inhibitors," Anna Cichonska, Balaguru Ravikumar, Robert J Allaway, Sungjoon Park, Fangping Wan, Olexandr Isayev, Shuya Li, Michael J Mason, Andrew Lamb, Minji Jeon, Sunkyu Kim, Mariya Popova, Jianyang Zeng, Kristen Dang, Gregory Koytiger, Jaewoo Kang, Carrow I Wells, Timothy M Willson, Tudor I Oprea, Avner Schlessinger, David H Drewry, Gustavo A Stolovitzky, Krister Wennerberg, Justin Guinney, Tero Aittokallio. bioRxiv, (2020)
  2. "Predicting Thermal Properties of Crystals Using Machine Learning," Sherif Abdulkader Tawfik, Olexandr Isayev, Michelle JS Spencer, David A Winkler. Advanced Theory and Simulations, 1900208, (2019)
  3. "Impressive computational acceleration by using machine learning for 2-dimensional super-lubricant materials discovery," Marco Fronzi, Mutaz Abu Ghazaleh, Olexandr Isayev, David A Winkler, Joe Shapter, Michael J Ford. arXiv preprint arXiv, 1911.11559 (2019)
  4. "The ANI-1ccx and ANI-1x data sets, coupled-cluster and density functional theory properties for molecules," Justin S Smith, Roman Zubatyuk, Benjamin T Nebgen, Nicholas Lubbers, Kipton Barros, Adrian Roitberg, Olexandr Isayev, Sergei Tretiak. ChemRxiv (2019)
  5. "Inter-Modular Linkers play a crucial role in governing the biosynthesis of non-ribosomal peptides," Sherif Farag, Rachel M Bleich, Elizabeth A Shank, Olexandr Isayev, Albert A Bowers, Alexander Tropsha. Bioinformatics, 35, 3584-3591, (2019)
Department of Chemistry, Physics, and Engineering, Chicago State University
Ph.D. Chemistry, University of Notre Dame, 2012

Understanding binding and structural properties of nanostructures that have important implications for increasing storage capacity in molecular electronics, minimizing high temperature destabilizing effects in energy systems, and maintaining bioactivity of bound molecules in biosensors are topics of interest in the group.  DNA origami nano technology, scanning microscopy (SEM and AFM), and electrochemistry are applicable techniques.

Department of Chemistry, University of Pittsburgh
University of Michigan, Ph.D. Chemistry, 2003

Our research involves the design and synthesis of novel hybrid inorganic-organic-biomolecule materials and studying, understanding, and precisely controlling their structures and properties. This research encompasses organic and inorganic synthesis, coordination chemistry, solid-state chemistry, biomolecule assembly, and nanoparticle synthesis and assembly.  We are particular motivated by applications related to the porosity of metal-organic framework materials (e.g. gas storage and separations) and the unique collective plasmonic properties of peptide-nanoparticle assemblies.

Most Cited Publications
  1. "Systematic design of pore size and functionality in isoreticular MOFs and their application in methane storage." Mohamed Eddaoudi, Jaheon Kim, Nathaniel Rosi, David Vodak, Joseph Wachter, Michael O'Keeffe, Omar M Yaghi. Science.
  2. "Nanostructures in biodiagnostics." Nathaniel L Rosi, Chad A Mirkin. Chemical reviews.
  3. "Hydrogen storage in microporous metal-organic frameworks." Nathaniel L Rosi, Juergen Eckert, Mohamed Eddaoudi, David T Vodak, Jaheon Kim, Michael O'Keeffe, Omar M Yaghi. Science.
  4. "Rod packings and metal− organic frameworks constructed from rod-shaped secondary building units." Nathaniel L Rosi, Jaheon Kim, Mohamed Eddaoudi, Banglin Chen, Michael O'Keeffe, Omar M Yaghi. Journal of the American Chemical Society.
  5. "Oligonucleotide-modified gold nanoparticles for intracellular gene regulation." Nathaniel L Rosi, David A Giljohann, C Shad Thaxton, Abigail KR Lytton-Jean, Min Su Han, Chad A Mirkin. Science.
Recent Publications
  1. "Design of Stratified Metal Organic Frameworks for Chemical Warfare Agent Concentration and Destruction." Jonathan Ruffley, Isabella Goodenough, Tianyi Luo, Dorian Thompson, Melissandre Richard, Nathaniel L Rosi, Eric Borguet, J Karl Johnson. 2019 AIChE Annual Meeting.
  2. "Au130− xAgx Nanoclusters with Non‐Metallicity: A Drum of Silver‐Rich Sites Enclosed in a Marks‐Decahedral Cage of Gold‐Rich Sites." Tatsuya Higaki, Chong Liu, David J Morris, Guiying He, Tian‐Yi Luo, Matthew Y Sfeir, Peng Zhang, Nathaniel L Rosi, Rongchao Jin. Angewandte Chemie International Edition.
  3. "Nanoparticle Doped PEDOT for Enhanced Electrode Coatings and Drug Delivery." Kevin M Woeppel, Xin Sally Zheng, Zachary M Schulte, Nathaniel L Rosi, Xinyan Tracy Cui. Advanced healthcare materials.
  4. "Tuning the Structure and Chiroptical Properties of Gold Nanoparticle Single Helices via Peptide Sequence Variation." Soumitra Mokashi-Punekar, Tiffany R Walsh, Nathaniel L Rosi. Journal of the American Chemical Society.
  5. "Fundamental Insights into the Reactivity and Utilization of Open Metal Sites in Cu(I)-MFU-4l." Lin Li, Yahui Yang, Mona H Mohamed, Sen Zhang, Götz Veser, Nathaniel L Rosi, J Karl Johnson. Organometallics.
Department of Chemistry, Carnegie Mellon University
Ph.D. Chemistry, Northwestern University, Illinois, 2003

Our research focuses on fundamental science and engineering questions motivated by the creation of materials on the nanometer scale (1 nm=10-9 m). Our research themes include the synthesis, characterization, and applications of nanoparticles (typically 1-100 nm in size). We are developing chemical methods for synthesizing well defined nanoparticles, including atomically precise nanoclusters, shape- and size-controlled nanocrystals, hybrid nano-architectures, and inorganic/polymer nanocomposites. In-depth characterizations of the physical and chemical properties of nanoparticles and self-assembled nanomaterials are carried out with microscopy and spectroscopy techniques, such as electron microscopy, atomic force microscopy, X-ray crystallography, steady-state and ultrafast spectroscopies, etc. We also develop applications of nanoparticles in areas of catalysis, optics, chemo- and bio-sensing, and photovoltaics, etc.

Selected Publications: 
  1. “Correlating second harmonic optical responses of single Ag nanoparticles with morphology”, Jin, R.; Jureller, J.E.; Kim, H.Y.; Scherer, N.F. J. Am. Chem. Soc.127, 12482 (2005).
  2. “Synthesis of open-ended, cylindrical Au-Ag alloy nanostructures on a Si/SiOx surface”, Zhang, H.; Jin, R.; Mirkin, C.A. Nano Lett., 4, 1493 (2004).
  3. “Thermally-induced formation of atomic Au clusters and conversion into nanocubes”, Jin, R.; Egusa, S.; Scherer, N.F. J. Am. Chem. Soc.126, 9900 (2004).
  4. “Controlling anisotropic nanoparticle growth through plasmon excitation”, Jin, R.; Cao, Y.W.;  Hao, E.; Metraux, G.S.; Schatz, G.C.; Mirkin, C.A.; Nature425, 487 (2003).
  5. “Raman dye-labeled nanoparticle probes for proteins”, Cao, Y.C.; Jin, R.; Nam, J.M.; Thaxton, C.S.; Mirkin, C.A. J. Am. Chem. Soc.125, 14676 (2003).
Most Cited Publications
  1. "Photoinduced conversion of silver nanospheres to nanoprisms", R Jin, YW Cao, CA Mirkin, KL Kelly, GC Schatz, JG Zheng, science, 294, 1901 (2001).
  2. "Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection", YWC Cao, R Jin, CA Mirkin, Science 297, 1536 (2002).
  3. "Controlling anisotropic nanoparticle growth through plasmon excitation", R Jin, YC Cao, E Hao, GS Métraux, GC Schatz, CA Mirkin, Nature 425, 487 (2003).
  4. "Correlating the crystal structure of a thiol-protected Au25 cluster and optical properties", M Zhu, CM Aikens, FJ Hollander, GC Schatz, R Jin, Journal of the American Chemical Society 130 , 5883 (2008).
  5. "What controls the melting properties of DNA-linked gold nanoparticle assemblies?", R Jin, G Wu, Z Li, CA Mirkin, GC Schatz, Journal of the American Chemical Society 125, 1643 (2003).
Recent Publications
  1. "Rational construction of a library of M29 nanoclusters from monometallic to tetrametallic." Kang, Xi, Xiao Wei, Shan Jin, Qianqin Yuan, Xinqi Luan, Yong Pei, Shuxin Wang, Manzhou Zhu, and Rongchao Jin. Proceedings of the National Academy of Sciences 116, no. 38 (2019): 18834-18840.
  2. "New Advances in Atomically Precise Silver Nanoclusters." Yang, Jie, and Rongchao Jin. ACS Materials Letters (2019).
  3. "Understanding the Solubility Behavior of Atomically Precise Gold Nanoclusters." Cowan, Michael J., Tatsuya Higaki, Rongchao Jin, and Giannis Mpourmpakis. The Journal of Physical Chemistry C 123, no. 32 (2019): 20006-20012.
  4. "Theoretical Prediction of Optical Absorption and Emission in Thiolated Gold Clusters." Day, Paul N., Ruth Pachter, Kiet A. Nguyen, and Rongchao Jin. The Journal of Physical Chemistry A 123, no. 30 (2019): 6472-6481.
  5. "Gold Nanoclusters: Bridging Gold Complexes and Plasmonic Nanoparticles in Photophysical Properties,"  M Zhou, C Zeng, Q Li, T Higaki, and R JinNanomaterials 9.7 (2019)

Highly Efficient Strategy for Constructing New Types of Peptide Macrocycles

  • By Burcu Ozden
  • 10 April 2018

Peng Liu and his colleagues report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalyzed intramolecular C(sp3)–H arylation reactions on their newly published paper in Nature Chemistry. 

This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures.

Department of Chemistry
PhD, Chemistry, Harvard University

Raúl Hernández Sánchez's research group is interested in combining supramolecular, inorganic, and materials chemistry to synthesize functional systems that bridge the gap between nanoscale materials and molecular chemistry. Their research is focused on developing new synthetic methodologies to access well-defined nanometer-sized clusters where they can investigate surface structure-function relationships relevant in catalytic and magnetic materials. Other efforts in the Hernández Sánchez (HS) group are aimed at designing and synthesizing structural analogues of carbon nanotubes where exquisite control of the resulting framework allows for properties manipulation.

Students in the HS group will engage in synthetic chemistry and develop familiarity with a range of spectroscopic, electrochemical, crystallographic and magnetic techniques. While rooted in synthetic chemistry, research in the HS group will interface with materials, organic, theory, and physical chemistry.

Most Cited Publications
  1. "High total proton conductivity in large-grained yttrium-doped barium zirconate," Y Yamazaki, R Hernandez-Sanchez, SM Haile, Chemistry of Materials 21, 2755 (2009
  2.  "Cation non-stoichiometry in yttrium-doped barium zirconate: phase behavior, microstructure, and proton conductivity," Y Yamazaki, R Hernandez-Sanchez, SM Haile, Journal of Materials Chemistry 20, 8158 (2010)
  3. "Disulfide Reductive Elimination From an Iron (III) Complex." Janice L. Wong, R Hernandez-Sanchez, Jennifer Glancy Logan, et. al.  Chemical Science 4.4 (2013)
  4. "Probing the role of an Fe IV Tetrazene in Catalytic Aziridination."  S Alan Cramer, R Hernandez-Sanchez, Desiraw F Brakhage, David M Jenkins.  Chemical Communications 50.90 (2014)
  5. "A Remarkably Active Iron Catecholate Catalyst Immobilized in a Porous Organic Polymer." Steven J. Kraft, R Hernandez-Sanchez, and Adam S Hock.  ACS Catalysis 3.5 (2013)
Recent Publications
  1. "Exposing the inadequacy of redox formalisms by resolving redox inequivalence within isovalent clusters," Bartholomew, A. K., Teesdale, J. J., Sánchez, R. H., Malbrecht, B. J., Juda, C. E., Ménard, G., ... & Sarangi, R. (2019).  Proceedings of the National Academy of Sciences116(32), 15836-15841.
  2. "Controlling Singlet Fission by Molecular Contortion," Conrad-Burton, Felisa S., Taifeng Liu, Florian Geyer, Roberto Costantini, Andrew P. Schlaus, Michael S. Spencer, Jue Wang et al. Journal of the American Chemical Society 141, no. 33 (2019): 13143-13147.
  3. "Defying strain in the synthesis of an electroactive bilayer helicene." Milton, Margarita, Nathaniel J. Schuster, Daniel W. Paley, Raúl Hernández Sánchez, Fay Ng, Michael L. Steigerwald, and Colin Nuckolls. Chemical Science (2018).
  4. "Thermally persistent high spin ground states in octahedral iron clusters." Hernández Sánchez, Raúl, and Theodore A. Betley. Journal of the American Chemical Society (2018).
  5. "Electron Cartography in Clusters." Raúl Hernández Sánchez, Anouck M Champsaur, Bonnie Choi, Suyin Grass Wang, et. al.  Angewande Chemie International 57.42 (2018)
Department of Chemistry, University of Pittsburgh
Ph.D. in Chemistry: Cornell University,1997

Saxena Group is focused on developing Fourier Transform electron spin resonance and its application to otherwise inaccessible problems in biophysics. 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. Saxena group creates the methods that measure the precise distance between two units in a protein, in order to determine their folding patterns and conformational dynamics. These ESR Spectroscopic Rulers— based on multiple quantum coherences and double resonance experiments—are unique in that they resolve distances in the 1-16 nm length scale even on bulk amorphous materials. Much of this work is based on the use of first-principles theory to develop new experimental protocols and to analyze experimental results.

His group continues to develop applications of these spectroscopic rulers that range from capturing the essence of structural changes - such as misfolding - in proteins, to measuring the atomic-level details of ion-permeation in a ligand gated ion-channel. The main projects of his group include:

  • Pulsed ESR methods to measure distance constraints in systems containing paramagnetic metals
  • Measurement of structural and dynamical determinants of the protein-DNA interactions and functional dynamics in pentameric ligand gated ion-channels.
  • Application of the spectroscopic ruler to measure and predict global structures of nanostructured materials.
  • Role of metals in aggregation of Amyloid-β peptide.
Most Cited Publications
  1. "Nonlinear-least-squares analysis of slow-motion EPR spectra in one and two dimensions using a modified Levenberg–Marquardt algorithm." David E Budil, Sanghyuk Lee, Sunil Saxena, Jack H Freed. Journal of Magnetic Resonance, Series A.
  2. "Amplification of xenon NMR and MRI by remote detection." Adam J Moulé, Megan M Spence, Song-I Han, Juliette A Seeley, Kimberly L Pierce, Sunil Saxena, Alexander Pines. Proceedings of the National Academy of Sciences.
  3. "Double quantum two-dimensional Fourier transform electron spin resonance: Distance measurements." Sunil Saxena, Jack H Freed. Chemical physics letters.
  4. "Theory of double quantum two-dimensional electron spin resonance with application to distance measurements." Sunil Saxena, Jack H Freed. The Journal of chemical physics.
  5. "Direct Evidence That All Three Histidine Residues Coordinate to Cu(II) in Amyloid-β1−16." Byong-kyu Shin, Sunil Saxena. Biochemistry.
Recent Publications
  1. "19F Paramagnetic Relaxation-Based NMR for Quaternary Structural Restraints of Ion Channels." Vasyl Bondarenko, Marta M Wells, Qiang Chen, Kevin C Singewald, Sunil Saxena, Yan Xu, Pei Tang. ACS chemical biology.
  2. "Effects of MnO2 of different structures on activation of peroxymonosulfate for bisphenol A degradation under acidic conditions." Jianzhi Huang, Yifan Dai, Kevin Singewald, Chung-Chiun Liu, Sunil Saxena, Huichun Zhang. Chemical Engineering Journal.
  3. "Designing Open Metal Sites in Metal–Organic Frameworks for Paraffin/Olefin Separations." Mona H Mohamed, Yahui Yang, Lin Li, Sen Zhang, Jonathan P Ruffley, Austin Gamble Jarvi, Sunil Saxena, Götz Veser, J Karl Johnson, Nathaniel L Rosi. Journal of the American Chemical Society.
  4. "An Undergraduate Experiment To Explore Cu (II) Coordination Environment in Multihistidine Compounds through Electron Spin Resonance Spectroscopy." Eugene P Wagner, Kai C Gronborg, Shreya Ghosh, Sunil Saxena. Journal of Chemical Education.
  5. "Innentitelbild: EPR Spectroscopy Detects Various Active State Conformations of the Transcriptional Regulator CueR (Angew. Chem. 10/2019)." Hila Sameach, Shreya Ghosh, Lada Gevorkyan‐Airapetov, Sunil Saxena, Sharon Ruthstein. Angewandte Chemie.

Molecular Phenotypes of Structurally Homologous ETS Transcriptions Factors

Gregory Poon
Thursday, September 28, 2017 - 4:30pm

 ETS transcription factors comprise an evolutionarily related family of genetic regulators that are ubiquitous in animals and control a myriad of physiologically critical processes. ETS proteins are united by a highly conserved DNA-binding domain, with overlapping target DNA preferences on the one hand, but are functionally diverse and non-redundant on the other. This so-called ìspecificity conundrumî besets not only our understanding of ETS homologs but also the structure-activity relationships of eukaryotic transcription factors in general. Translationally, it hampers efforts to develop...