Prof. Dan Thomas Major

Associate Professor
Prof. Dan Thomas Major
Reception hours: 
Guiding the research students: 



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.



  • 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.



  • 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 (
  • Theoretical study of photovoltaics



  1. Levy, N.; Mahammed, A.; Kosa, M.; Major, D. T.; Gross, Z.; Elbaz, L. Development of metal-corroles as alternative non-precious metal catalysts (NPMCs) for oxygen reduction. Angew. Chem. Int. Ed. 2015 Accepted.
  2. 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 Accepted.
  3. 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 Accepted.
  4. 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. 2015 Accepted.
  5. 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 Accepted.
  6. Markovsky, B.; 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.; Lampert, J.; Volkov, A.; Shin, J.; Garsuch, A. Studies of Aluminum-Doped LiNi0.5Co0.2Mn0.3O2: Electrochemical Behavior, Aging, Structural Transformations, and Thermal Characteristics. J. Electrochem. Soc. 2015 Accepted.
  7. 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 Accepted.
  8. Engel, H.; Eitan, R.; Azuri, A.; Major, D. T. Nuclear Quantum Effects in Chemical Reactions via Higher-Order Path-Integral Calculations. Chem. Phys. 2015 Accepted.
  9. Nitoker, N.; Major, D. T. Understanding the Reaction Mechanism and Intermediate Stabilization in Serine Racemase Using Multiscale Quantum-Classical Simulations. Biochemistry 2015, 54, 516-527.
  10. 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. 2015, 11, 64-72.
  11. 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 2015, 119, 906-916 (Invited paper, Jorgensen Festschrift).
  12. 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. 2015, 17, 295-298.
  13. 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 2014, 30, 13596-13605.
  14. 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. 2014, 54, 62-79 (Invited paper).
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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).
  21. 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).
  22. 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.
  23. 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 Science. 2013, 6, 3046-3053.!divAbstract
  24. 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 2013, 117, 17919–17926.
  25. 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.
  26. 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.
  27. 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.
  28. 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, 8, 4786-4796.
  29. 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. 2012, 8, 2484-2496.
  30. 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. 2012, 17, 861-879.
  31. 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. 2012, 8, 1223–1234.
  32. 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 2012, 116, 770-782.
  33. 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. 2012, 33, 435-441.
  34. 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.
  35. 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.
  36. 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. 2011, 100, 4390-4400.
  37. 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. 2011, 133, 6270-6278.
  38. 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. 2011, 7, 1273-1286.
  39. 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. European Journal of Medicinal Chemistry 2011, 46, 447-467.
  40. 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. Organic and Biomolecular Chemistry 2010, 8, 4637-3652.
  41. 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.
  42. Weitman, M.; Major, D. T. Challenges posed to bornyl diphosphate synthase: Diverging reaction mechanisms in monoterpenes. J. Am. Chem. Soc. 2010, 132, 6349-6360.
  43. 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.
  44. 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 2010, 66, 1465-1471.
  45. 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. 2010, 342, 283-292.
  46. 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.
  47. Rubinstein, A.; Major, D. T. Catalyzing racemizations in the absence of a cofactor: The reaction mechanism in proline racemase. J. Am. Chem. Soc. 2009, 131, 8513-8521.
  48. 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.
  49. 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. 2008, 29, 514-522.
  50. Braverman, S.; Pechenick-Azizi, T.; Major, D. T.; Sprecher, M. b-Halo-a,b-Unsaturated g-Sultones. J. Org. Chem. 2007, 72, 6824-6831.
  51. 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. 2007, 3, 949-960.
  52. 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. 2006, 128, 16345-16357.
  53. Major, D.T.; Nam, K.; Gao, J. Transition State Stabilization and a-Amino Acidity in Alanine Racemase. J. Am. Chem. Soc. 2006, 128, 8114-8115.
  54. Gao, J.; Ma, S.; Major, D.T.; Nam, K.; Pu, J.; Truhlar, D. G. Mechanism and Free Energies of Enzymatic Reactions. Chem. Rev. 2006, 106, 3188-3209 (Invited paper).
  55. 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. 2006, 2, 236-245.
  56. 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. 2005, 127, 16374-16375.
  57. Major, D.T.; Gao, J. Implementation of the bisection sampling method in path-integral simulations. J. Mol. Graph. Mod. 2005, 24, 121-127 (Invited paper for special issue in honor of Prof. Ian Hillier).
  58. 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. 2004, 47, 4405-4416.
  59. Major, D. T.; Fischer, B. Molecular recognition in purinergic receptors. 1. A comprehensive computational study of the h-P2Y(1)-receptor. J. Med. Chem. 2004, 47, 4391-4404.
  60. Major, D. T.; Fischer, B. Theoretical study of the pH-dependent photophysics of N1,N6-ethenoadenine and N3,N4-ethenocytosine. J. Phys. Chem. A. 2003, 107, 8923-8931.
  61. Major, D. T.; Laxer, A.; Fischer, B. Protonation studies of modified adenine and adenine nucleotides by theoretical calculations and 15N NMR. J. Org. Chem. 2002, 67, 790-802.
  62. 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. 2001, 66, 5463-5481.
  63. 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. 1999, 42, 5338-5347.
  64. 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. 1999, 42, 5325-5337.
  65. 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. 1999, 42, 2685-2696.


Book Chapters

  1. 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.
  2. 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., RCS Publishing; CITY, 105-131, 2009.
  3. 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, The Humana Press Inc.; Totwa, NJ, 2007.


  1. Introduction to quantum chemistry
  2. Quantum chemistry and spectroscopy
  3. Computational chemistry
  4. Mathematical models in chemistry (molecular modeling)


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 (
  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



Research Group

The Major research group:


Head of group:

Dan T Major (


Current members:

Monica Kosa ( (Post-doc)

Alina Osnis ( (Post-doc)

Alexandra Vardi ( (Post-doc)

Reuven Eitan ( (Post-doc)

Dvir Doron ( (PhD Student)

Tali Engel ( (PhD student)

Yehoshua Freud ( (MSc student)

Neta Nitoker ( (MSc student)

Yaron Pshetitsky ( (MSc student)

Haim Sazan ( (MSc student)


Former members:

Michal Weitman ( (Post-doc)

Hila Marciano ( (MSc student)

Karin Povolzki ( (MSc student)

Daniel Roston (Visiting student)

Asaf Azuri (MSc student)

Amir Rubinstein (MSc student)


The group: