Prof. Menachem (Hemi) Gutman
Ph.D.: Hebrew University, Jerusalem, Israel 1968
Phone: Tel: +972-3-6409875
Fax: +972-3-6409875
E-mail: me@hemi.tau.ac.il
Room#: Sherman Building, Room 510
Member's portrait

Research Interests

The Laser Laboratory for Fast Reactions in Biology is an active research group, headed by Menachem (Hemi) Gutman, and includes Dr. Esther Nachliel, Dana Bar-On, Limor Radozkocwicz, Lihie Levin, Ortal Amber-Vitus, and Nataly Kurchenko.

The research in the group combines experimental measurements, detailed kinetic analysis and theoretical interpretation of the results.

Former members of our research group (from the near past) include Dr. Ran Friedman, Dr. Assaf Ganoth, Dr. Aviv Mezer, Dr. Elad project, Dr. Eran Bosis and Dr. Adel Abramowitz.

  

The Laser Laboratory for Fast Reactions in Biology has been active, since 1979, in kinetic measurements of proton transfer reactions, utilizing the kinetic parameters for probing the interface between bio-molecules and the water. The experimental system was based on photo-excitation of photo acid molecules driving a sub-nanosecond acidification of the solution. The observations consisted of fast (microsecond) and ultra fast (picoseconds) fluorescence and absorbance transitions, which were analyzed through integration of differential rate equations. These measurements were applied for probing defined spaces like the active site of proteins, the inter-membrane space in multi-lamellar bodies, the inner aqueous body of a reversed micelles and the solvation layer of protein.

During the last ten years, the main line of the research is gradually shifting towards detailed understanding of molecular events at atomic resolution using molecular dynamics techniques coupled with experimental measurement. These lines of research are exemplified by the following research topics and the resulting publication:

  1.  Optimization and evaluation of the Force Field parameters [1, 2].
  2. Study of the effect of the solvent on the conformation, dynamics and the reactivity of small molecules in solution [3-5].
  3. Evaluation of the molecular mechanism of proton transfer between reactants, based on real time measurement [5-14].
  4. The interaction of specific regulatory and carrier proteins with fatty acid molecules [15-18].
  5. Dynamics simulations of the exocytotic mechanism and the dynamics of the cis SNARE formation [9, 19-23].
  6. Kinetic analysis of complex dynamics processes and application of Genetic Algorithm as a search strategy [9, 19, 24-26]
  7. Role of glycosylation in the quality control of protein folding[25].
  8. The role of Calmodulin in mechano-chemical reactions and in the extra-cellular cytoplasmic signal transduction [27-29].
  9. The role of electrostatic forces in the binding of regulatory proteins to the membrane [26].
  10. Molecular dynamics simulations of the signaling mechanism of Rho proteins [30].

The present subjects under investigation are:

  1. The mechanism of proton transfer inside the Coulomb cage. A research carried out in collaboration with Prof. D. Huppert, School of Chemistry.
  2. Modeling the kinetics of complex intra-cellular processes (exocytosis, SNARE complex formation and post translational Quality Control of protein folding) through numeric integration of differential rate equations. These studies are carried out in collaboration with Dr. U. Asheri, Life sciences.
  3. Modeling the interactions of protein with  PIP containing membranes  (collaboration with Prof. Uri Asheri, Dr. Gali Prag, Life sciences,  and Prof. Emad Tajkhorshid, Beckman institute, University of Illinois.
  4. Stochastic modeling of interactions between membranal proteins and the dynamics of raft formation (collaboration with Prof. U. Asheri, Life sciences).
  5. Molecular dynamics simulations of protein-ligand and protein-protein (collaboration with Dr. A. Azem, Life Sciences).
  6. Quantification of the structural likeness between short peptides and specific domains on designated proteins (collaboration with Dr. Y. Tsfadia and Prof. J. Gershoni, Life sciences).
  7. The dynamics of interaction between small ampiphilic molecules with carrier proteins (collaboration with Dr. Y. Tsfadia, Life sciences).
    8. Conformational transformation of  membranal proteins (collaborative study with Dr. Yossi Tsfadia, life sciences, and Dr. Yulia Einav (Holon Institute of Technology).


Selected Publications
  1. Project E, Nachliel E, Gutman M: Parameterization of Ca+2-protein interactions for molecular dynamics simulations. J Comput Chem 2008, 29(7):1163-1169.
  2. Project E, Nachliel E, Gutman M: Force field-dependent structural divergence revealed during long time simulations of Calbindin d9k. J Comput Chem 2009, 31(9):1864-1872.
  3. Radoszkowicz L, Huppert D, Nachliel E, Gutman M: Sampling the conformation space of FAD in water-methanol mixtures through molecular dynamics and fluorescence measurements. J Phys Chem A 2010, 114(2):1017-1022. e-format
  4. Radoszkowicz L, Presiado I, Erez Y, Nachliel E, Huppert D, Gutman M: Time-resolved emission of flavin adenine dinucleotide in water and water-methanol mixtures. Phys Chem Chem Phys 2011, 13(25):12058-1206
  5. Radozkowicz L, Project E, Gepshtein R, Nachliel E, Huppert D, Gutman M: The Effect of Environment on the Dynamics of Proton Dissociation in Water. Zeitschrift Fur Physikalische Chemie-International Journal of Research in Physical Chemistry & Chemical Physics 2008, 222(8-9):1247-1262.
  6. Agmon N, Gutman M: Bioenergetics: Proton fronts on membranes. Nature Chemistry  2011, 3(11):840-842.
  7. Gutman MN, E.: Proton transfer at the Protein-Water  interface. In: Hydrogen Transfer Reactions. Edited by Hynes JTK, J.P. Limbach, H.H. Schowen, R.L., vol. 4. Weinheim: Wiley-VCH Verlag GmbH &Co.; 2007: 1499-1529.
  8. Friedman R, Fischer S, Nachliel E, Scheiner S, Gutman M: Minimum energy pathways for proton transfer between adjacent sites exposed to water. J Phys Chem B 2007, 111(21):6059-6070. e-format 
  9. Mezer A, Ashery U, Gutman M, Project E, Bosis E, Fibich G, Nachliel E: Systematic search for the rate constants that control the exocytotic process from chromaffin cells by a genetic algorithm. Biochim Biophys Acta 2006, 1763(4):345-355. e-format
  10. Gutman M, Nachliel E, Friedman R: The mechanism of proton transfer between adjacent sites on the molecular surface. Biochim Biophys Acta 2006, 1757(8):931-941. e-format 
  11. Gutman M, Nachliel E, Friedman R: The dynamics of proton transfer between adjacent sites. Photochem Photobiol Sci 2006, 5(6):531-537. e-format 
  12. Gepshtein R, Leiderman P, Huppert D, Project E, Nachliel E, Gutman M: Proton antenna effect of the gamma-cyclodextrin outer surface, measured by excited state proton transfer. J Phys Chem B 2006, 110(51):26354-26364. e-format
  13. Mezer A, Friedman R, Noivirt O, Nachliel E, Gutman M: The mechanism of proton transfer between adjacent sites exposed to water. J Phys Chem B 2005, 109(22):11379-11388. e-format
  14. Friedman R, Nachliel E, Gutman M: Application of classical molecular dynamics for evaluation of proton transfer mechanism on a protein. Biochim Biophys Acta 2005, 1710(2-3):67-77. e-format
  15. Levin LB, Ganoth A, Amram S, Nachliel E, Gutman M, Tsfadia Y: Insight into the interaction sites between fatty acid binding proteins and their ligands. J Mol Model 2010, 16(5):929-938. e-format 
  16. Levin LB, Nachliel E, Gutman M, Tsfadia Y: Molecular dynamics study of the interaction between fatty acid binding proteins with palmitate mini-micelles. Mol Cell Biochem 2009, 326(1-2):29-33. e-format
  17. Friedman R, Nachliel E, Gutman M: Fatty acid binding proteins: same structure but different binding mechanisms? Molecular dynamics simulations of intestinal fatty acid binding protein. Biophys J 2006, 90(5):1535-1545. e-format
  18. Friedman R, Nachliel E, Gutman M: Molecular dynamics simulations of the adipocyte lipid binding protein reveal a novel entry site for the ligand. Biochemistry 2005, 44(11):4275-4283. e-format
  19. Mezer A, Bosis E, Ashery U, Nachliel E and Gutman M: A Comprehensive kinetic Model of the Exocytotic Process: Evaluation of the Reaction Mechanism. RECOMB 2005 Ws in Regolatory Gemonics 2007, LNBI 4023:249-257.
  20. Mezer A, Nachliel E, Gutman M, Ashery U: Exocytosis: Threading of the partial reactions into a functional kinetic mechanism. Neural Plasticity 2003, 10(3).
  21. Mezer A, Nachliel E, Gutman M, Ashery U: A new platform to study the molecular mechanisms of exocytosis. J Neurosci 2004, 24((40):8838-8846. e-format
  22. Bar-On D, Winter U, Nachliel E, Gutman M, Fasshauer D, Lang T, Ashery U: Imaging the assembly and disassembly kinetics of cis-SNARE complexes on native plasma membranes. FEBS Lett 2008, 582(23-24):3563-3568. e-format
  23. Bar-On D, Gutman M, Mezer A, Ashery U, Lang T, Nachliel E: Evaluation of the heterogeneous reactivity of the syntaxin molecules on the inner leaflet of the plasma membrane. J Neurosci 2009, 29(39):12292-12301. e-format
  24. Moscovitch D, Noivirt O, Mezer A, Nachliel E, Mark T, Gutman M, Fibich G: Determination of a unique solution to parallel proton transfer reactions using the genetic algorithm. Biophys J 2004, 87(1):47-57. e-format
  25. Bosis E, Nachliel E, Cohen T, Takeda Y, Ito Y, Bar-Nun S, Gutman M: Endoplasmic reticulum glucosidase II is inhibited by its end products. Biochemistry 2008, 47(41):10970-10980. e-format
  26. Sengupta P, Bosis E, Nachliel E, Gutman M, Smith SO, Mihalyne G, Zaitseva I, McLaughlin S: EGFR juxtamembrane domain, membranes, and calmodulin: kinetics of their interaction. Biophys J 2009, 96(12):4887-4895. e-format
  27. Ganoth A, Nachliel E, Friedman R, Gutman M: Myosin V movement: lessons from molecular dynamics studies of IQ peptides in the lever arm. Biochemistry 2007, 46(50):14524-14536. e-format
  28. Ganoth A, Nachliel E, Friedman R, Gutman M: Molecular dynamics study of a calmodulin-like protein with an IQ peptide: spontaneous refolding of the protein around the peptide. Proteins 2006, 64(1):133-146.
  29. Ganoth A, Friedman R, Nachliel E, Gutman M: A molecular dynamics study and free energy analysis of complexes between the Mlc1p protein and two IQ motif peptides. Biophys J 2006, 91(7):2436-2450.
  30. Abramovitz A, Gutman M, Nachliel E: Structural coupling between the Rho–insert domain of Cdc42 and the Geranylgeranyl binding site of RhoGDI. Biochemistry 2012, in press
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