Prof. Dan Thomas Major

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Full Professor
Telephone
Fax
972-3-7384053
Email
majort@biu.ac.il
Office
Chemistry Bldg. (211) Room 301. Laboratory Phone: 972-3-5317684
Reception Hours
Anytime
CV

ACADEMIC BACKGROUND

Prof. Major completed his undergraduate studies in chemistry and computer sciences at Bar-Ilan University in 1997. He received his Ph.D. from Bar-Ilan University in 2003 under Prof. Bilha Fischer. During his Ph.D. he worked on molecular properties of nucleotide derivatives, theoretical modeling of G-protein coupled receptors, as well as molecular recognition.

He did a post-doctorate at the University of Minnesota under Prof. Jiali Gao during the years 2003-2006. During his post-doctorate he was involved in development and application of theoretical methods for enzyme catalysis.

Since 2007 he is a Faculty member in the Chemistry Department at Bar-Ilan University. His main research interests are in the field of computational chemistry, computational biochemistry, and computational nanotechnology.

 

ACADEMIC AWARDS AND DISTINCTIONS

  • Excellence in teaching, Rector’s Office, Bar-Ilan University, 2016.
  • Krill Prize (Wolf Foundation), 2009.
  • Alon Fellowship, 2008-2010.
  • Fulbright Scholarship, 2003-2004.
  • Excellence in teaching, Rector’s Office, Bar-Ilan University, 2001.
  • Eshkol Scholarship, 2000-2003.
  • Excellent young scientist from the Israeli Chemical Society, 2001.
  • Moris Benin Prize, 1999.
  • Bar-Ilan University Chemistry Department Prize, 1998.
  • Wolf Foundation Prize, young scientist, 1998.
  • Rachel and Reuven Jacobs Prize, 1997.

 

RESEARCH INTERESTS

  • Theoretical study of enzymatic and solution-phase reactions using state-of-the-art combined quantum mechanics/molecular mechanics Hamiltonians
  • Molecular Dynamics and Monte Carlo simulations of proteins
  • Development of novel path-integral simulation methodology for the investigation of quantum nuclear effects in solution phase and enzymatic reactions
  • Development of hybrid quantum mechanics/molecular mechanics Hamiltonians
  • High-level quantum mechanical calculations of small biomolecules
  • Molecular modeling of membrane proteins
  • Docking studies of protein-ligand interactions
  • Theoretical study of Lithium batteries properties (http://www.inrep.co.il)
  • Theoretical study of photovoltaics

 

LINKS

Research
Computational Chemistry, Computational Biochemistry, Computational Nanotechnology
  1. Development of quantum simulation tools for nuclear quantum effects in enzyme catalysis. This entails development of new path-integral methods for the simulations of zero-point energy and tunneling effects in condensed phase environments. Several new methods are being developed and are incorporated into simulation platforms for enzymatic reactions.
  2. Development of hybrid quantum mechanics/molecular mechanics methods. This includes the development of specific reaction parameter semi-empirical Hamiltonians for use in enzyme simulations. Additionally, we also develop novel perturbation approaches wherein a low-level Hamiltonian is perturbed into a higher level one with a view to enhance accuracy at a reduced computational cost.
  3. Study dynamical effects and tunnelling in enzyme catalysis through hydrogen transfer reactions. This involves studying several important enzyme systems such as the hydride transfer in dihydrofolate reductase and formate dehydrogenase.
  4. Enzyme mechanisms through heavy atom kinetic isotope effects. This approach entails the study of the reaction mechanism in deaminase and decarboxylase enzymes via heavy atom kinetic isotope effects.
  5. Enzyme mechanisms in a variety of systems, such as
    • Terpenes (monoterpenes and sesquiterpenes)
    • Racemases (alanine racemase, proline racemase, serine racemase)
    • Dihydrofolate reductase and formate dehydrogenase
  6. Properties of functional surface groups in self-assembled monolayers. This project includes the computation of the pH-dependent vibrational spectrum of carboxylate terminated monolayers via novel QM/MM applications in combination with molecular dynamics simulations.
  7. Properties of cathode material in lithium batteries using density functional theory approaches (http://www.inrep.co.il)
  8. Properties of solar cell materials using density functional theory approaches

 

Research Gallery

 

DHFR quantum simulations: Open path-integral simulations of transferring hydride

 

Alanine racemase simulations: Free energy simulations

 

QM/MM region in the monoterpene enzyme bornyl diphosphate

 

Docked structures in Nitroalkane Oxidase using hybrid QM/MM NOE based MD docking

 

Comparisons of X-ray structure and docked structure in Nitroalkane Oxidase

 

 

Publications

Articles

  1. Raz, K.; Levi, S.; Gupta, P. K.; Major, D. T. Enzymatic Control of Product Distribution in Terpene Synthases: Insights from Multiscale Simulations. Curr. Opin. Biotech. 2020 Accepted.
  2. Levi, S.; Zhang, Q.; Major, D. T. Thermodynamic and Kinetic Control Determine Sesquiterpene Reaction Pathways inside Nano Capsules. ACS Catal. 2020, 10, 6843-6853.
  3. Perkal, O.; Qasem, Z.; Turgeman, M.; Schwartz, R.; Gevorkyan-Airapetov, L.; Pavlin, M.; Magistrato, A.; Major, D. T.; Ruthstein, S. Cu(I) controls conformational states in human Atox1 metallochaperone: An EPR and multiscale simulation study. J. Phys. Chem. B 2020, 124, 4399-4411.
  4. Syntrivanis, L-. D.; Nemethova, I.; Schmid, D.; Levi, S.; Prescimone, A.; Bissegger, F.; Major, D. T.; Tiefenbacher, K. Four-step access to the sesquiterpene natural product presilphiperfolan-1β-ol and unnatural derivatives via supramolecular catalysis. J. Am. Chem. Soc. 2020, 142, 5896-5900.
  5. Kannath, S.; Adamczyk, P.; Ferro-Costas, D.; Fernandez-Ramos, A.; Major, D. T.; Dybala-Defratyka, A. The Role of Microsolvation and Quantum Effects in the Accurate Prediction of Kinetic Isotope Effects: the Case of Hydrogen Atom Abstraction in Ethanol by Atomic Hydrogen in Aqueous Solution. J. Chem. Theory Comput. 2020, 16, 847-859.
  6. Chakraborty, A.; K, S.; Kumar, S.; Markovsky, B.; Aurbach, A.; Dixit, M.; Major, D. T. Layered Cathode Materials for Lithium-Ion Batteries: Review of Computational Studies on LiNi1-x-yCoxMnyO2 and LiNi1-x-yCoxAlyO2Chem. Mater. 2020, 32, 915-952.
  7. Raz, K.; Driller, R.; Brueck, T.; Loll, B.; Major, D. T. Understanding the Role of Active Site Residues in CotB2 Catalysis Using a Cluster Model. Beilstein J. Org. Chem. 2020, 16, 50-59.
  8. Chakraborty, A.; Kunnikuruvan, S.; Dixit, M.; Major, D. T. Review of computational studies of NCM cathode materials for Li-ion Batteries. Accepted Isr. J. Chem. 2020.
  9. Khamaru, N.; De, S.; Das, A.; Singh, V.; Major, D. T.; Dasgupta, P.; Das, D.; Chatterjee, S. Effects of Cu-doping on the structural and magnetic properties of 1-D chain compound MnV2O6J. Magn. Magn. Mater. 2020, 497, 165995.
  10. Driller, R.; Garbe, D.; Mehlmer, N.; Fuchs, M.; Raz, K.; Major, D. T.; Brück, T.; Loll, B. CotB2, a versatile terpene synthase: mechanistic and structural insights into an exciting protein. Beilstein J. Org. Chem. 2019, 15, 2355-2368.
  11. Shpilman, J. S.; Friedman, A.; Zion, N.; Levy, N.; Major, D. T.; Elbaz, L. Combined Experimental and Theoretical Study of Cobalt Corroles as Catalysts for Oxygen Reduction Reaction. J. Phys. Chem. C 2019, 123, 30129-30136.
  12. Pagano, P.; Guo, Q.; Ranhasinghe, C.; Schroeder, E.; Robben, K.; Häse, F.; Ye, H.; Wickersham, K.; Aspuru-Guzik, A.; Major, D. T.; Gakhar, L.; Kohen, A.; Cheatum, C. M. Oscillatory Active-site Motions Correlate with Kinetic Isotope Effects in Enzymes. ACS Catal. 20199, 11199-11206.
  13. Das, S.; Shimshi, M.; Raz, K.; Nitoker, N.; Mhashal, A.; Ansbacher, T.; Major, D. T. EnzyDock: Protein-Ligand Docking of Multiple Reactive States Along a Reaction Coordinate in Enzymes. J. Chem. Theory Comput. 2019, 15, 5116-5134.
  14. Susai, F.; Kovacheva, D.; Chakraborty, A.; Kravchuk, T.; Ravikumar, R.; Talianker, M.; Grinblat, J.; Burstein, L.; Kauffmann, Y.; Major, D. T.; Markovsky, B.; Aurbach, D. Improving performance of LiNi0.8Co0.1Mn0.1O2 cathode materials for Lithium-Ion Batteries by doping with Mo ions: theoretical and experimental studies. ACS Appl. Energy Mater2019, 2, 4521-4534.
  15. Pahima, E.; Zhang, Q.; Tiefenbacher, K.; Major, D. T. Discovering Monoterpene Catalysis Inside Nano-capsules with Multiscale Modeling and Experiments. J. Am. Chem. Soc. 2019, 141, 6234-6246.
  16. Chang, Z.; Ansbacher, T.; Zhang, L.; Liu, W.; Ko, T.-P., Huang, J.-W.; Dai, L.; Guo, R.-T.; Major, D. T.; Chen, C.-C. Crystal structure of LepI, a SAM-dependent multi-functional enzyme in leporin biosynthesis. Org. Biomol. Chem. 2019, 17, 2070-2076.
  17. Wolf, T.; Kumar, S.; Singh, H.; Aussenac, F.; Frenkel, A. I.; Major, D. T.; Leskes, M. Endogenous Dynamic Nuclear Polarization for Natural Abundance 17O and Lithium NMR in the Bulk of Inorganic Solids. J. Am. Chem. Soc. 2019, 141, 451-462.
  18. Pahima, E.; Hoz, S.; Ben-Tzion, M.; Major, D. T. Computational Design of Biofuels from Terpenes and Terpenoids. Sustain. Energy Fuels 2019, 3, 457-466.
  19. Mhashal, A. R.; Pshetitsky, Y.; Cheatum, C. M.; Kohen, A.; Major, D. T. Evolutionary Effects on Bound Substrate pKa in Dihydrofolate Reductase. J. Am. Chem. Soc. 2018140, 16650-16660.
  20. Chakraborty, A.; Dixit, M.; Major, D. T. Predicting Accurate Cathode Properties of Layered Oxide Materials Using the SCAN Meta-GGA Density Functional. npj Comput. Mater. 20184, 60.
  21. Driller, R.; Janke, S.; Fuchs, M.; Warner, E.; Mhashal, A. R.; Major, D. T.; Christmann, M.; Brück, T.; Loll, B. Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis. Nat. Commun. 20189, 3971.
  22. Breuer, O.; Chakraborty, A.; Liu, J.; Kravchuk, T.; Burstein, L.; Grinblat, J.; Kauffman, Y.; Gladkih, A.; Zuberi, M.; Nayak, P.; Frenkel, A. I.; Talianker, M.; Major, D. T.; Markovsky, B.; Aurbach, D. Understanding the Role of Minor Molybdenum Doping in LiNi0.5Co0.2Mn0.3OElectrodes: from Structural and Surface Analyses and Theoretical Modeling to Practical Electrochemical Cells. ACS Appl. Mater. & Interfaces 2018, 10, 29608-29621.
  23. Major, D. T. Complex Terpenes in One Pot. Nat. Catal. 20181, 567-568.
  24. Mhashal, A. R.; Pshetitsky, Y.; Eitan, R.; Cheatum, C. M.; Kohen, A.; Major, D. T. Effect of Asp122 Mutation on the Hydride Transfer in E. Coli DHFR Demonstrates the Goldilocks of Enzyme Flexibility. J. Phys. Chem. B 2018,122, 8006-8017.
  25. Kosa, M.; Levy, N.; Elbaz, L.; Major, D. T. Theoretical Study of the Electrocatalytic Reduction of Oxygen by Metallocorroles. J. Phys. Chem. C 2018122, 17686-17694.
  26. Fishman Jacob, T.; Singh, V.; Dixit, M.; Ginsburg-Shmuel, T.; Fonseca, B.; Pintor, J.; Youdim, M. B. H.; Major, D. T.; Weinreb, O.; Fischer, B. A Highly Promising Drug Candidate for the Treatment of Glaucoma Based on a P2Y6-Receptor Agonist. Purinergic Signal. 2018, 14, 271-284.
  27. Ansbacher, T.; Freud, Y.; Major, D. T. Slow Starter Enzymes: Role of Active Site Architecture in the Catalytic Control in the Biosynthesis of Taxadiene by Taxadiene Synthase. Biochemistry 201857, 3773-3779.
  28. Jun, D. W.; Kim, U. H.; Park, K. J.; Aurbach, D.; Major, D. T.; Goobes, G.; Dixit, M.; Leifer, N.; Wang, C.; Yan, P.; Ahn, D.; Kim, K. H.; Yoon, C. S.; Sun, Y. Y. Pushing the limit of layered transition metal oxide cathodes for high-energy density rechargeable Li ion batteries. Energy Environ. Sci. 2018, 11, 1271-1279.
  29. Das, S.; Nam, K.; Major, D. T. Rapid Convergence of Energy and Free Energy Profiles with QM Size in QM/MM Simulations of Proton Transfer in DNA. J. Chem. Theory Comp. 2018, 14, 1695-1705.
  30. Bauer, P.; Barrozo, A. H.; Amrein, B. A.; Purg, M.; Esguerra, M.; Wilson, P. B.; Major, D. T.; Åqvist, J.; Kamerlin, S. C. L. Q6: A comprehensive toolkit for empirical valence bond and related free energy calculations. SoftwareX 20187, 388-395.
  31. Dixit, M.; Weitman, M.; Gao, J.; Major, D. T. Comment on “Substrate Folding Modes in Trichodiene Synthase: A Determinant of Chemo- and Stereoselectivity”. ACS Catal2018, 8, 1371-1375.
  32. Levy, N.; Shpilman, J. S.; Honig, H.; Major, D. T.; Elbaz, L. Surprising Substituent Effect in Corroles on the Electrochemical Activation of Oxygen Reduction. Chem. Comm. 2017, 53, 12942-12945.
  33. Dixit, M.; Markovsky, B.; Schipper, F.; Aurbach, D.; Major, D. T. The Origin of Structural Degradation During Cycling and Low Thermal Stability of Ni-rich Layered Transition Metal-Based Electrode Materials. J. Phys. Chem. C. 2017, 121, 22628-22636.
  34. Freud, Y.; Ansbacher, T.; Major, D. T. Catalytic control in the facile proton transfer in taxadiene synthase. ACS Catal. 2017, 7, 7653-7657.
  35. Rozental, E.; Altus, E.; Major, D. T.; Hoz, S. Shaping Polyyne Rods by an Electric Field. ChemistryOpen 2017, 6, 733-738.
  36. Schipper, F.; Bouzaglo, H.; Dixit, M.; Erickson, E. M.; Weigel, T.; Talianker, M.; Grinblat, J.; Burstein, L.; Schmidt, M.; Lampert, J.; Erk, C.; Markovsky, B.; Major, D. T.; Aurbach, D. From Surface ZrO₂ Coating to Bulk Zr Doping by High Temperature Annealing of Nickel Rich Materials and their Enhanced Electrochemical Performance in Lithium Ion Batteries. Adv. Ener. Mater. 2017, 1701682.
  37. Major, D. T. Electrostatic Control of Chemistry in Terpene Cyclases. ACS Catal. 2017, 7, 5461-5465.
  38. Mhashal, A.; Vardi-Kilshtain, A.; Kohen, A.; Major, D. T. The Role of the M20 Loop in the Hydride Transfer in E. Coli Dihydrofolate Reductase. J. Biol. Chem. 2017, 292, 14229-14239.
  39. Schipper, F.; Nayak, P. K.; Erickson, E. M.; Amalraj, S. F.; Srur-Lavi, O.; Penki, T. R.; Talianker, M.; Grinblat, J.; Sclar, H.; Breuer, O.; Julien, C. M.; Munichandraiah, N.; Kovacheva, D.; Dixit, M.; Major, D. T.; Markovsky, B.; Aurbach, D. Study of cathode materials for Lithium-ion batteries: Recent progress and new challenges. Inorganics 2017, 5, 32.
  40. Dixit, M.; Markovsky, B.; Aurbach, D.; Major, D. T. Unraveling the Effects of Al Doping on the Electrochemical Properties of LiNi0.5Co0.2Mn0.3O2 Using First Principles. J. Electrochem. Soc. 2017, 164, A6359-6365.
  41. Dixit, M.; Weitman, M.; Gao, J.; Major, D. T. Chemical Control in the Battle Against Fidelity in Promiscuous Natural Product Biosynthesis: The Case of Trichodiene Synthase. ACS Catalysis 2017, 7, 812-818.
  42. Majhi, K.; Singh, V.; Rietwyk, K. J.; Keller, D. A.; Barad, H. N.; Ginsburg, A.; Yan, Z.; Anderson, A. Y.; Zaban, A.; Major, D. T. Electron-Hybridization Induced Enhancement of Photo Activity in Indium-Doped Co3O4. J. Phys. Chem. C 2016, 120, 28983-28991.
  43. de la Llave, E.; Talaie, E.; Levi, E.; Kumar, P.; Dixit, M.; Rao, P. T.; Hartmann, P.; Chesneau, F. F.; Major, D. T.; Greenstein, M.; Aurbach, D.; Nazar, L. F. Improving Energy Density and Structural Stability of Manganese Oxide Cathodes for Na-ion Batteries by Structural Lithium Substitution. Chem. Mater. 2016, 28, 9064-9076.
  44. Schipper, F.; Dixit, M.; Kovacheva, D.; Talianker, M.; Haik, O.; Grinblat, Y.; Erikson, E. M.; Ghanty, C.; Major, D. T.; Markovsky, B.; Aurbach, D. Stabilizing Nickel-Rich Layered Cathode Materials by a High-Charge Cation Doping Strategy: Zirconium-Doped LiNi0.6Co0.2Mn0.2O2. J. Mater. Chem. A 2016, 4, 16073-16084.
  45. Salama, M.; Shtrenberg, I.; Gizbar, H.; Nitoker, N.; Kosa, M.; Adamsky, K. K.; Ari, M.; Shimon, L. J. W.; Gottilieb, H. E.; Major, D. T.; Gofer, Y.; Aurbach, D. Unique Behavior of dimethoxyethane (DME)/Mg(N(SO2CF3)2)2 Solutions. J. Phys. Chem. C 2016, 120, 19586-19594.
  46. Pshetitsky, Y.; Eitan, R.; Verner, G.; Kohen, A.; Major, D. T. Improved Sugar Puckering Profiles for Nicotinamide Ribonucleoside for Hybrid QM/MM Simulations. J. Chem. Theory Comp. 2016, 12, 5179-5189.
  47. Das, S.; Dixit, M.; Major, D. T. First Principles Model Calculations of the Biosynthetic Pathway in Selinadiene Synthase. Bioorg. Med. Chem. 2016, 24, 4867-4870.
  48. Dixit, M.; Das, S.; Mhashal, A. R.; Eitan, R.; Major, D. T. Practical aspects of multiscale classical and quantum simulations of enzyme reactions. Methods in Enzymology 2016, 577, 251-286 (Invited review).
  49. Guo, Q.; Gakhar, L.; Wickersham, K.; Francis, K.; Vardi-Kilshtain, A.; Major, D. T.; Cheatum, C.; Kohen, A. Structural and Kinetic Studies of Formate Dehydrogenase from Candida boidinii. Biochemistry 2016, 55, 2760-2771.
  50. Levi Hevroni, B.; Major, D. T.; Dixit, M.; Mhashal, A. R.; Das, S.; Fischer, B. Nucleoside-2’,3’/3’,5’-Bis(thio)phosphate are Zn(II)/Cu(II)-Chelators Capable of Disassembly of Amyloid Beta(1-42)–Zn(II)/Cu(II) Aggregates. Org. Biomol. Chem. 2016, 14, 4640-4653.
  51. Dutta, P.; Pramanick, S.; Singh, V.; Major, D. T.; Das, D.; Chatterjee, S. Anomalous magnetotransport behavior in Fe doped MnNiGe alloys. Phys. Rev. B 2016, 93, 134408.
  52. Singh. V.; Major, D. T. Electronic Structure and Bonding in Co-based Single and Mixed Valence Oxides: A Chemical Perspective from First Principles. Inorg. Chem. 2016, 55, 3307-3315.
  53. Dixit, M.; Major, D. T.; Pal, S. Hydrogen adsorption in ZIF-7: A DFT and ab-initio molecular dynamics study. Chem. Phys. Lett. 2016, 651, 178-182.
  54. Kosa, M.; Aurbach, D.; Major, D. T. First-principles evaluation of the inherent stabilities of pure LixMPO4 (M=Mn, Fe, Co,) and Mixed Binary LixFeyM'1-yPO4 (M'=Mn, Co) Olivine Phosphates. Mater. Chem. Phys. 2016, 174, 54-58.
  55. Singh, V.; Dixit, M.; Kosa, M.; Major, D. T.; Levi, E.; Aurbach, D. Is it true that the normal valence-length correlation is irrelevant for metal-metal bonds? Chem. Eur. J. 2016, 22, 5269-5276.
  56. Dixit, M.; Kosa, M.; Srur Lavi, O.; Markovsky, B.; Aurbach, D.; Major, D. T. Electrochemical and Kinetic Studies of LiNi0.5Co0.2Mn0.3O2 as a Positive Electrode Material for Li-ion Batteries using First Principles. Phys. Chem. Chem. Phys. 2016, 18, 6799-6812.
  57. Kosa, M.; Barad, H.; Singh, V.; Keller, D.; Shimanovich, K.; Rühle, S.; Anderson, A.; Zaban, A.; Major, D. T. A Combined Computational and Experimental Investigation of Mg Doped α-Fe2O3. Phys. Chem. Chem. Phys. 2016, 18, 781-791.
  58. Singh, V.; Gershinsky, Y.; Kosa, M.; Dixit, M.; Zitoun, D.; Major, D. T. Magnetism in olivine-type LiCo1-xFexPO4 cathode materials: Bridging theory and experiment. Phys. Chem. Chem. Phys. 201517, 31202 - 31215.
  59. Azran, S.; Danino, O.; Förster, D.; Kenigsberg, S.; Reiser, R.; Dixit, M.; Singh, V.; Major, D. T.; Fischer, B. Identification of Highly Promising Anti-Oxidants / Neuroprotectants Based on Nucleoside 5’-Phosphorothioate Scaffold. Synthesis, Activity, and Mechanisms of Action. J. Med. Chem. 201558, 8427-8443.
  60. Levy, N.; Mahammed, A.; Kosa, M.; Major, D. T.; Gross, Z.; Elbaz, L. Metal-corroles as non-precious metal catalysts for oxygen reduction. Angew. Chem. Int. Ed. 2015, 54, 14080-14084.
  61. Eizig, Z.; Major, D. T.; Kasdan, H. L.; Afrimzon, E.; Zurgil, N.; Deutsch, M. Analysis of the spectroscopic Aspects of the Cationic Dye Basic Orange 21. J. Phys. Chem. A 2015, 119, 9794-9804.
  62. Dixit, M.; Engel, H.; Eitan, R.; Aurbach, D.; Levi, M.; Kosa, M.; Major, D. T. Classical and Quantum Modeling of Li and Na Diffusion in FePO4. J. Phys. Chem. C 2015, 119, 15801-15809.
  63. Sayer, A. H.; Blum, E.; Major, D. T.; Vardi-Kilshtain, A.; Levi-Hevroni, B.; Fischer, B. Adenosine/Guanosine-3',5’-Bis-Phosphate as Biocompatible and Selective Zn2+-Ion Chelators. Characterization and Comparison with Adenosine/Guanosine-5’-Di-Phosphate. Dalton Trans. 201544, 7305-7317.
  64. Vardi-Kilshtain, A.; Nitoker, N.; Major, D. T. Nuclear Quantum Effects and Kinetic Isotope Effects in Enzyme Reactions. Archives of Biochemistry and Biophysics. Invited Review. 2015, 582, 18-27.
  65. Aurbach, D.; Srur-Lavi, O.; Ghanty, C.; Dixit, M.; Haik, O.; Talianker, M.; Grinblat, J.; Leifer, N.; Lavi, R.; Major, D. T.; Goobes, G.; Zinigrad, E.; Erickson, E.; Kosa, M.; Markovsky, B.; Lampert, J.; Volkov, A.; Shin, J. -Y.; Garsuch, A. Studies of Aluminum-Doped LiNi0.5Co0.2Mn0.3O2: Electrochemical Behavior, Aging, Structural Transformations, and Thermal Characteristics. J. Electrochem. Soc. 2015162, A1014-A1027.
  66. Pariente-Cohen, N.; Weitman, M.; Major, D. T.; Gottlieb, H.; Hoz, S.; Nudelman, A. Acylation or Phosphorylation of Hydroxyurea Unexpectedly Take Place on N rather than on O, Leading to the Formation of Amides Instead of the Expected Esters. RCS Advances 2015, 5, 24038-24043.
  67. Engel, H.; Eitan, R.; Azuri, A.; Major, D. T. Nuclear Quantum Effects in Chemical Reactions via Higher-Order Path-Integral Calculations. Chem. Phys. 2015, 450-451, 95-101.
  68. Nitoker, N.; Major, D. T. Understanding the Reaction Mechanism and Intermediate Stabilization in Serine Racemase Using Multiscale Quantum-Classical Simulations. Biochemistry 201554, 516-527.
  69. Singh, V.; Kosa, M.; Majhi, K.; Major, D. T. Putting DFT to the test: A first principles study of electronic, magnetic and optical properties of Co3O4. J. Chem. Theory Comp. 201511, 64-72.
  70. Doron, D.; Stojkovic, V.; Gakhar, L.; Kohen, A.; Major, D. T. Free Energy Simulations of Active-Site Mutants of Dihydrofolate Reductase. J. Phys. Chem. B 2015119, 906-916(Invited paper, Jorgensen Festschrift).
  71. Kosa, M.; Major, D. T. Structural Trends in Hybrid Perovskites, [Me2NH2] M [HCOO]3 (M=Mn, Fe, Co, Ni, Zn). Computational Assessment Based on Bader Charge Analysis. Crystal Eng. Comm. 201517, 295-298.
  72. Toledano, T.; Sazan, H.; Barnea-Nehoshtan, L.; Mukhopadhyay, S.; Alon, H.; Lerman, K.; Bendikov, T.; Major, D. T.; Sukenik, C.; Vilan, A.; Cahen, D. Odd-Even Effect in Molecular Electronic Transport via an Aromatic Ring. Langmuir 201430, 13596-13605.
  73. Carvalho, A. T. P.; Barrozo, A.; Doron, D.; Vardi Kilshtain, A.; Major, D. T.; Kamerlin, S. C. L. Challenges in Computational Studies of Enzyme Structure, Function and Dynamics. J. Mol. Graph. Mod. 201454, 62-79 (Invited paper).
  74. Yeung, H. H.-M.; Kosa, M.; Griffin, J. M.; Grey, C. P.; Major, D. T.; Cheetham, A. K. Topotactic elimination of water across a C-C ligand bond in a dense 3-D metal-organic framework. Chem. Comm. 2014, 50, 13292-13295.
  75. Kovaliov, M.; Weitman, M.; Major, D. T.; Fischer, B. Phenyl-Imidazolo-Cytidine Analogues: Structure-Photophysical-Activity Relationship and Potential Use for SNP Typing. J. Org. Chem. 2014, 79, 7051-7062.
  76. Gat, Y.; Vardi-Kilshtain, A.; Grossman, I.; Major, D. T.; Fass, D. Enzyme structure captures four cysteines aligned for disulfide relay. Protein Sci. 2014, 23, 1102-1112.
  77. Roston, D.; Kohen, A.; Doron, D.; Major, D. T. Simulations of Remote Mutants of Dihydrofolate Reductase Reveal the Nature of a Network of Residues Coupled to Hydride Transfer. J. Comput. Chem. 2014, 35, 1411-1417.
  78. Doron, D.; Kohen, A.; Nam, K.; Major, D. T. How accurate are transition states from simulations of enzymatic reactions? J. Chem. Theory Comput. 2014, 10, 1863-1871.
  79. Major, D. T.; Freud, Y.; Weitman, M. Catalytic Control in Terpenoid Cyclases: Multiscale Modeling of Thermodynamic, Kinetic, and Dynamic Effects. Curr. Opin. Chem. Biol. 2014, 21, 25-33 (Invited paper).
  80. Doron, D.; Weitman, M.; Vardi-Kilshtain, A.; Azuri, A.; Engel, H.; Major, D. T. Multi-scale quantum-classical simulations of enzymes. Isr. J. Chem. 2014 Accepted (Invited paper).
  81. Zilbershtein-Shklanovsky , L.; Weitman, M.; Major, D. T.; Fischer, B. Rules for the design of highly fluorescent nucleoside probes - 8-(substituted cinnamyl)-adenosine analogues. J. Org. Chem. 2013, 78, 11999-12008.
  82. Buhbut, S.; Clifford, J. N.; Kosa, M.; Anderson, A.; Shalom, M.; Major, D. T.; Palomares, E.; Zaban, A. Controlling dye aggregation, injection energetics, and catalytic recombination in organic sensitizer based dye cells using a single electrolyte additive. Energy & Environmental Science20136, 3046-3053. http://pubs.rsc.org/en/content/articlelanding/2013/ee/c3ee41486h#!divAbstract
  83. Osnis, A.; Kosa, M.; Aurbach, D.; Major, D. T. A systematic first-principles investigation of mixed transition metal olivine phosphates LiM1-yM’yPO4 (M/M’=Mn, Fe, Co) as cathode materials. J. Phys. Chem. C 2013117, 17919–17926. http://pubs.acs.org/doi/abs/10.1021/jp402755r
  84. Vardi-Kilshtain, A.; Doron, D.; Major, D. T. Quantum and classical simulations of orotidine monophosphate decarboxylase: Support for a direct decarboxylation mechanism. Biochemistry 2013, 52, 4382-4390. http://pubs.acs.org/doi/abs/10.1021/bi400190v
  85. Pour, N.; Gofer, Y.; Major, D. T.; Keinan-Adamsky, K.; Gottlieb, H.; Aurbach, D. Multinuclear magnetic resonance spectroscopy and density functional theory calculations for the identification of the equilibrium species in THF solutions of organo-metallic complexes suitable as electrolyte solutions for rechargeable Mg batteries. Organometallics 2013, 32, 3165-3173. http://dx.doi.org/10.1021/om300865a
  86. Major, D. T.; Weitman, M. Electrostatically Guided Dynamics - the Root of Fidelity in a Promsicuous Terpene Synthase? J. Am. Chem. Soc. 2012,134, 19454-19462. http://dx.doi.org/10.1021/ja308295p
  87. Vardi-Kilshtain, A.; Major, D. T.; Kohen, A.; Engel, H.; Doron, D. Hybrid Quantum and Classical Simulations of the Formate Dehydrogenase Catalyzed Hydride Transfer Reaction on an Accurate Semi-Empirical Potential Energy Surface.  J. Chem. Theory Comput. 2012, accepted. http://dx.doi.org/10.1021/ct300628e
  88. Doron, D.; Kohen, A.; Major, D. T. Collective Reaction Coordinate for Hybrid Quantum and Molecular Mechanics Simulations: A Case Study of the Hydride Transfer in Dihydrofolate Reductase. J. Chem. Theory Comput. 20128, 2484-2496.http://pubs.acs.org/doi/abs/10.1021/ct300235k
  89. Stern, N.; Major, D. T.; Gottlieb, H. E.; Weizman, D.; Fischer, B. Speciation and Characterization by Potentiometric Titrations, NMR, and Molecular Dynamics Simulations.J. Biol. Inorg. Chem. 201217, 861-879. http://www.springerlink.com/content/0949-8257/10.1007/s00775-012-0903-2
  90. Engel, H.; Doron, D.; Kohen, A.; Major, D. T. Momentum Distribution as a Fingerprint of Quantum Delocalization in Enzymatic Reactions: Open-Chain Path-Integral Simulations of Model Systems and the Hydride Transfer in Dihydrofolate Reductase. J. Chem. Theory Comput. 20128, 1223–1234. http://pubs.acs.org/doi/abs/10.1021/ct200874q
  91. Osnis, A.; Sukenik, C. N.; Major, D. T. Structure of Carboxyl Acid Terminated Self-Assembled Monolayers from Molecular Dynamics Simulations and Hybrid Quantum Mechanics-Molecular Mechanics Vibrational Normal Mode Analysis. J. Phys. Chem. C 2012116, 770-782. http://pubs.acs.org/doi/abs/10.1021/jp208443u
  92. Vardi-Kilshtain, A.; Azuri, A.; Major, D. T. Path-Integral Calculations of Heavy Atom Kinetic Isotope Effects in Condensed Phase Reactions Using Gradient-Based Forward Corrector Algorithms. J. Comp. Chem. 201233, 435-441. http://onlinelibrary.wiley.com/doi/10.1002/jcc.21986/abstract
  93. Doron, D.; Major, D. T.; Kohen, A.; Thiel, W.; Wu, X. Hybrid quantum and classical simulations of the dihydrofolate reductase catalyzed hydride transfer reaction on an accurate semi-empirical potential energy surface. J. Chem. Theory Comput. 2011, 7, 3420-3437. http://pubs.acs.org/doi/abs/10.1021/ct2004808
  94. Lin, Y. L.; Gao, J.; Rubinstein, A.; Major, D. T. Molecular Dynamics Simulations of the Intramolecular Proton Transfer and Carbanion Stabilization in the Pyridoxal 5-phosphate Dependent Enzymes L-Dopa Decarboxylase and Alanine Racemase. Invited review. BBA Proteins and Proteomics. 2011, 1814, 1438-1446. http://dx.doi.org/10.1016/j.bbapap.2011.05.002
  95. Margulis-Goshen, K.; Weitman, M.; Major, D. T.; Magdassi, S. Celecoxib nanoparticles formed from volatile microemulsions: an inhibitory effect of glycyrrhizinate on crystallization in aqueous medium. J. Pharm Sci. 2011100, 4390-4400. http://onlinelibrary.wiley.com/doi/10.1002/jps.22623/abstract
  96. Pour, N.; Gofer, Y. Major, D. T.; Aurbach, D. Structural Analysis of Electrolyte Solutions for Rechargeable Mg Batteries Comprising Magnesium-Aluminate Chloro-Phenyl Complexes by Electrochemical, Spectroscopic, Diffractometric means and DFT Calculations. J. Am. Chem. Soc. 2011133, 6270-6278. http://pubs.acs.org/doi/abs/10.1021/ja1098512
  97. Azuri, A.; Engel, H.; Doron, D.; Major, D. T. Path-Integral Calculations of nuclear quantum effects in model systems, small molecules, and enzymes via gradient-based forward corrector algorithms. J. Chem. Theory Comput. 20117, 1273-1286. http://pubs.acs.org/doi/abs/10.1021/ct100716c
  98. Weitman, M.; Lerman, K.; Nudelman, A.; Major D. T.; Hizi, A.; Herschhorn, A. Structure-Activity Relationship Studies of 1-(4-Chloro-2,5-dimethoxyphenyl)-3-(3-propoxypropyl)thiourea, a Non-nucleoside Reverse Transcriptase Inhibitor of Human Immunodeficiency Virus Type-1. Eur. J. Med. Chem. 201146, 447-467. http://dx.doi.org/10.1016/j.ejmech.2010.11.003
  99. Stern, N.; Major, D. T.; Gottlieb, H. E.; Weizman, D.; Fischer, B. What is the Conformation of Physiologically-Active Dinucleoside Polyphosphates in an Aqueous Solution? Conformational Analysis of Free Dinucleoside Polyphosphates by NMR and Molecular Dynamics Simulations. Org. Biomol. Chem. 2010, 8, 4637-3652. http://pubs.rsc.org/en/content/articlehtml/2010/ob/c005122e
  100. Rubinstein, A.; Major, D. T. Understanding catalytic specificity in alanine racemase from Quantum Mechanical and Molecular Mechanical simulations of the arginine 219 mutant. Biochemistry 2010, 49, 3957-3964. http://pubs.acs.org/doi/abs/10.1021/bi1002629
  101. Weitman, M.; Major, D. T. Challenges posed to bornyl diphosphate synthase: Diverging reaction mechanisms in monoterpenes. J. Am. Chem. Soc. 2010, 132, 6349-6360. http://pubs.acs.org/doi/abs/10.1021/ja910134x
  102. Gabashvili, A.; Major, D. T.; Perkas, N.; Gedanken, A. The sonochemical synthesis and characterization of mesoporous chiral titania using a chiral inorganic precursor. Ultrason. Sonochem. 2010, 17, 605-609. http://dx.doi.org/10.1016/j.ultsonch.2009.10.019
  103. Weitman, M.; Lerman, L.; Nudelman, A.; Major, D. T.; Gottlieb, H. E. Synthesis of imidazoles and oxazoles by the Bredereck reaction. Facile structural elucidation based on 13C-NMR and carbon satellites in the 1H-NMR spectra. Tetrahedron 201066, 1465-1471. http://dx.doi.org/10.1016/j.tet.2009.12.019
  104. Margulis-Goshen, K.; Netivi, H.; Major, D. T.; Gradzielski, M.; Raviv, U.; Magdassi, S. Formation of organic nanoparticles from volatile microemulsions. J. Colloid Interface Sci. 2010342, 283-292. http://dx.doi.org/10.1016/j.jcis.2009.10.024
  105. Major, D. T.; Heroux, A.; Orville, A. M.; Valley, M. P.; Fitzpatrick, P. F.; Gao, J. Differential quantum mechanical tunneling in the uncatalyzed and in the Nitroalkane Oxidase proton abstraction of nitroethane. Proc. Nat. Acad. Sci. U.S.A. 2009, 106, 20734-20739. http://www.pnas.org/content/106/49/20734.full
  106. Rubinstein, A.; Major, D. T. Catalyzing racemizations in the absence of a cofactor: The reaction mechanism in proline racemase. J. Am. Chem. Soc. 2009131, 8513-8521. http://pubs.acs.org/doi/abs/10.1021/ja900716y
  107. Nizri, G.; Lagerge, S.; Kamyshny, A.; Major, D. T.; Magdassi, S. Polymer-Surfactant Interactions: Binding mechanism of Sodium Dodecyl Sulfate to Poly(diallyldimethylammonium chloride). J. Colloid Interface Sci. 2008, 320, 74-81. http://dx.doi.org/10.1016/j.jcis.2008.01.016
  108. Gao, J.; Wong, K.-Y.; Major, D. T. Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water. J. Comput. Chem. 200829, 514-522. http://onlinelibrary.wiley.com/doi/10.1002/jcc.20810/abstract
  109. Braverman, S.; Pechenick-Azizi, T.; Major, D. T.; Sprecher, M. b-Halo-a,b-Unsaturated g-Sultones. J. Org. Chem. 200772, 6824-6831. http://pubs.acs.org/doi/abs/10.1021/jo071085q
  110. Major, D.T.; Gao, J. An Integrated Path Integral and Free Energy Perturbation-Umbrella Sampling Method for Computing Kinetic Isotope Effects of Chemical Reactions in Solutions and in Enzymes. J. Chem. Theory Comput. 20073, 949-960. http://pubs.acs.org/doi/abs/10.1021/ct600371k
  111. Major, D.T.; Gao, J. A Combined QM/MM Study of the Reaction Mechanism and a-Amino Acidity in Alanine Racemase. J. Am. Chem. Soc. 2006128, 16345-16357. http://pubs.acs.org/doi/abs/10.1021/ja066334r
  112. Major, D.T.; Nam, K.; Gao, J. Transition State Stabilization and a-Amino Acidity in Alanine Racemase. J. Am. Chem. Soc. 2006128, 8114-8115. http://pubs.acs.org/doi/abs/10.1021/ja062272t
  113. Gao, J.; Ma, S.; Major, D.T.; Nam, K.; Pu, J.; Truhlar, D. G. Mechanism and Free Energies of Enzymatic Reactions. Chem. Rev. 2006106, 3188-3209 (Invited paper). http://pubs.acs.org/doi/abs/10.1021/cr050293k
  114. Major, D.T.; Garcia-Viloca, M.; Gao, J. Path-integral simulations of proton transfer reactions in aqueous solution using a combined QM/MM potential. J. Chem. Theory Comput. 20062, 236-245. http://pubs.acs.org/doi/abs/10.1021/ct050257t
  115. Major, D.T.; York, D. M.; Gao, J. Solvent polarization and kinetic isotope effects in nitroethane deprotonation and implications to the nitroalkane oxidase reaction.  J. Am. Chem. Soc. 2005127, 16374-16375. http://pubs.acs.org/doi/abs/10.1021/ja055881u
  116. Major, D.T.; Gao, J. Implementation of the bisection sampling method in path-integral simulations. J. Mol. Graph. Mod. 200524, 121-127 (Invited paper for special issue in honor of Prof. Ian Hillier). http://dx.doi.org/10.1016/j.jmgm.2005.04.002
  117. Major, D. T.; Nahum, V.; Wang, Y. F.; Reiser, G.; Fischer, B. Molecular recognition in purinergic receptors. 2. Diastereoselectivity of the h-P2Y(1)-receptor. J. Med. Chem. 200447, 4405-4416. http://pubs.acs.org/doi/abs/10.1021/jm049771u
  118. Major, D. T.; Fischer, B. Molecular recognition in purinergic receptors. 1. A comprehensive computational study of the h-P2Y(1)-receptor. J. Med. Chem. 200447, 4391-4404. http://pubs.acs.org/doi/abs/10.1021/jm049772m
  119. Major, D. T.; Fischer, B. Theoretical study of the pH-dependent photophysics of N1,N6-ethenoadenine and N3,N4-ethenocytosine. J. Phys. Chem. A. 2003107, 8923-8931. http://pubs.acs.org/doi/abs/10.1021/jp0340515
  120. Major, D. T.; Laxer, A.; Fischer, B. Protonation studies of modified adenine and adenine nucleotides by theoretical calculations and 15N NMR. J. Org. Chem. 200267, 790-802. http://pubs.acs.org/doi/abs/10.1021/jo0107554
  121. Laxer, A.; Major, D. T.; Gottlieb, H. E.; Fischer, B. (15N (5))-labeled adenine derivatives: Synthesis and studies of tautomerism by 15N NMR spectroscopy and theoretical calculations. J. Org. Chem. 200166, 5463-5481. http://pubs.acs.org/doi/abs/10.1021/jo010344n
  122. Major, D. T.; Halbfinger, E.; Fischer, B. Molecular Recognition of Modified Adenine Nucleotides by the P2Y1-Receptor. Part II. A Computational Approach. J. Med. Chem. 199942, 5338-5347. http://pubs.acs.org/doi/abs/10.1021/jm9901576
  123. Fischer, B.; Halbfinger, E.; Major, D. T.; Ritzmann, M.; Ubl, J. J.; Reiser, G.; Boyer, J. L.; Harden, K. T. Molecular recognition of modified adenine nucleotides by the P2Y1-receptor. Part I. A synthetic, biochemical and NMR approach. J. Med. Chem. 199942, 5325-5337. http://pubs.acs.org/doi/abs/10.1021/jm990156d
  124. Fischer, B.; Yefidoff, R.; Major, D. T.; Rutman-Halili, I.; Shneyvays, V.; Zinman, T.; Jacobson, K. A.; Shainberg A. Characterization of ‘mini-nucleotides’ as P2X-receptor agonists in rat cardiocytes culture. An integrated synthetic, biochemical and theoretical study. J. Med. Chem. 199942, 2685-2696. http://pubs.acs.org/doi/abs/10.1021/jm990085i

 

Book Chapters

  1. Major, D. T.; Eitan, R.; Das, S.; Mhashal, A.; Singh, V. Nuclear Quantum Effects in Enzymatic Reactions. In Simulating Enzyme Reactivity, Editor Tunon, I.; Moliner, V. pp. 340-374, RCS Publishing; Cambridge, UK, 2017.
  2. Wong, K.-Y.; Song, L.; Xie, W.; Major, D. T.; Lin, Y.-L.; Cembran, A.; Gao, J. Quantum Mechanical Methods for Biomolecular Simulations. in Multi-Scale Quantum Models for Biocatalysis. Modern Techniques and Applications, Editor York, D. M., Lee, T. -S., pp. 79-101, Springer; Netherlands, 2009.
  3. Gao, J.; Wong, K.-Y.; Major, D. T.; Cembran, A.; Song, L.; Lin, Y.-L.; Fan, Y.; Ma, S. Kinetic Isotope Effects from Hybrid Classical and Quantum Path-Integral Simulations. in Quantum Tunnelling in Enzyme-Catalyzed Reactions, Editor Scrutton, N. S.; Allemann, R. K., pp. 105-131, RCS Publishing; Cambridge, UK, 2009.
  4. Gao, J.; Major, D. T.; Fan, Y.; Lin, Y.-L.; Ma, S.; Wong, K.-Y. Hybrid Quantum and Classical Methods for Computing Kinetic Isotope Effects of Reactions in Solution and in Enzymes. in Molecular Modeling of Proteins, Editor Andreas Kukol, pp. 36-72, The Humana Press Inc.; Totwa, NJ, 2007.
Courses
  1. Introduction to quantum chemistry
  2. Quantum chemistry and spectroscopy
  3. Computational chemistry
  4. Mathematical models in chemistry (molecular modeling)
Research Group

The Major research group:

 

Head of group:

Dan T Major (majort@biu.ac.il)

 

Current members:

Prashant Gupta (prashantguptajk@gmail.com) (Post-doc)

Arup Chakraborty (arupchakraborty719@gmail.com) (Post-doc)

Sooraj K (soorajk@biu.ac.il) (Post-doc)

Ortal Marciano (ortal94@gmail.com) (Post-doc)

Yaron Pshetitsky (yaron.pshetitsky@live.biu.ac.il) (PhD student)

Keren Raz (keren1.raz@gmail.com) (PhD student)

Shani Levi (levishani94@gmail.com) (PhD student)

Masha Nihamkin (mash.1992@gmail.com) (PhD student)

Renana Schwartz (renana164@gmail.com) (MSc student)

Reem Tarabeh (reemtarabeh1997@gmail.com) (MSc student)

Maor Ben Noach (bennoachmaor@gmail.com) (MSc student)

Efrat Pahima (faywood00@gmail.com) (Research associate)

Jennifer Shulamit Shpilman (jencolo@hotmail.com) (Research associate)

 

Former members:

Mudit Dixit (dixitmuditk@gmail.com) (Post-doc)

Anil Mhashal (anil2000.2008@gmail.com) (Post-doc)

Susanta Das (susanta.chemistry@gmail.com) (Post-doc)

Vijay Singh (singhvijay31@gmail.com) (Post-doc)

Sandeep Kumar (sandeepk.phy@gmail.com) (Post-doc)

Tamar Ansbacher (tamar.ansbacher@mail.huji.ac.il) (Post-doc)

Michal Weitman (weitmanm@gmail.com) (Post-doc)

Monica Kosa (monica.kosa.shtaif@gmail.com) (Post-doc)

Alexandra Vardi (alex_vardi@yahoo.com) (Post-doc)

Reuven Eitan (reuven.eitan@gmail.com) (Post-doc)

Alina Osnis (alina_roz@hotmail.com) (PhD student)

Dvir Doron (Dvir.Doron@biu.ac.il) (PhD Student)

Tali Engel (tali_engel@yahoo.com) (PhD student)

Efrat Pahima (faywood00@gmail.com) (MSc student)

Jennifer Shulamit Shpilman (jencolo@hotmail.com) (MSc student)

Hila Marciano (hilanidam@gmail.com) (MSc student)

Karin Povolzki (karinpovolozki512@gmail.com) (MSc student)

Yehoshua Freud (shuafreud@gmail.com) (MSc student)

Neta Nitoker (n.nitoker@gmail.com) (MSc student)

Yaron Pshetitsky (yaron.pshetitsky@live.biu.ac.il) (MSc student)

Haim Sazan (haim.sazan@gmail.com) (MSc student)

Daniel Roston (Visiting student)

Asaf Azuri (MSc student)

Amir Rubinstein (MSc student)

 

The group: