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  • Prof.  Avital Shurki
Prof.  Avital Shurki
Research Interests
The main objective of the research is to understand fundamental questions in chemistry and biochemistry using different computational methods. It is a theoretical research, which applies quantum-mechanical (QM) approaches, molecular mechanical (MM) approached as well as hybrid QM/MM computational schemes. Several specific projects are on going:

Method Development

The 2013 Nobel prize in Chemistry, which was awarded for "the development of multiscale models for complex chemical systems", has highlighted the great impact of computational methods in the field of  biochemistry. Recent years have witnessed significant contributions of computational methods both  as tools for understanding the molecular details of biological processes as well as predictive tools. For example, computational strategies combined with experiments proved to be very successful for enzyme engineering in recent years. Yet, the rate enhancement of the enzymatic reaction resulting from these strategies is usually relatively modest and we would like to improve it.
One of the major requirements for the successes of computational methods is the reliability of the results and the insights gained from them. Thus, we have developed a new hybrid Quantum-Mechanics Molecular Mechanics (QM/MM) method where the QM part is treated by ab-initio Valence Bond (VB)  theory. This VB/MM method has the advantages of the well established Empirical VB (EVB) methodology but provides better accuracy. In it’s simplest form, VB theory is used on a daily basis by all chemists, as it constitutes the “language” of chemical drawings (Lewis structures, resonance structures etc). The VB/MM method we developed therefore keeps these insights of VB but allows calculations of processes within proteins without the requirement to parameterize the QM part. Further development of the method however is required as VB is currently limited to relatively small systems. We plan to push VB to  the limits and define its current status while trying to extend it to larger and more complex systems.
It is our hope that one of the outcomes of this work will be the ability to utilize VB/MM and provide VB analysis which will be used for better understanding of any biological reaction.

Enzyme Design

Computer based enzyme design, which involves creating an enzyme from scratch to catalyze any pre-chosen reaction is one of the greatest challenges available to date. Thus far the emphasis in that field was placed mainly on stabilizing the structure of the protein and little effort was invested on the actual  catalysis. We are developing a new concept to design reactivity which is base on valence bond (VB) methodology. We have developed a methodology that provides better  description of enzyme catalysis by analyzing the chemical role of each amino acid. The method was shown to facilitate predictions of "correct" rate enhancing mutations.
The scheme was tested and proved to be working in the first step of the conversion of methylchloride to  alcohol in haloalkane dehalogenase, leading to two successful predictions with considerable calculated  rate enhancement. We are currently working on substrates that their conversion into alcohols leads to  two different enentiomers, while trying to enhance both the rate and the selectivity of the enzyme towards one enentiomer. We plan to study various other enzymatic reactions (e.g., Ras/RasGAP) with  mutations that are known to impair the reaction and try to suggest new mutations for improved catalytic activity. Our ultimate goal is to be able eventually to design any enzyme at will.


Copper ions do not appear in a free aquated form in biological systems due to their possible toxicity. Therefore, another project focuses on copper metallochaperones proteins found to be responsible for carrying copper(I) ions to the designated locations while preventing undesired and toxic chemistry. This project involves studying the mechanism of copper binding and exchange by these proteins using computational methods and tries to understand what prevents the copper from leaving its metallochaperone to the solution.

Mechanistics Studies

We study the mechanistic details of various different systems including the hydrolysis of GTP vy various G-Proteins, hydrolysis of Organo-phosphate esters by ButyrylColineEsterase and its mutants, Conversion of Halo-alkanes into Alcohols in Haloalkane-Dehalogenaze etc.


Cannabinoids and/or endocannabinoids belong to a very large class of chemical compounds with diverse activity within our body including appetite stimulation, motor control, anxiety and depression attenuation, and relief to an array of symptoms such as pain, nausea, and inflammation. The variance in their activity is suggested to stem from the fact that different compounds from this class promote distinct conformations of canabinoid receptors, which may result in different signaling pathways (also called biased signaling). As such, these compounds have great potential therapeutic benefits. However, the molecular mechanisms underlying this differential signaling and its regulation by different ligands are not fully understood and are the main goal of our study. We try to understand the relation between the binding mode and the resulting conformational change and thus the resulting signalling pathway. Based on our studies we should be able to develop of pathway-biased ligands, which have great potential for the development of selective therapeutic agents.
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Group Members
Dr. Rajapandian Varatharaj
Dr. Mukesh Chourasia
Dr. Hemant Srivastava
Dr. Moshe Amitai
Dr. Avital Sharir-Ivry
LAB Phone Numbers:
+972-2-765-7351 (87351)
+972-2-765-7495 (87495)
Available positions
A position is available for excellent Ph.D. students and postdocs interested to study biological systems using theoretical methods. The projects will focus on developement of new approach for enzyme design, mechanisms of enzymatic catalysis or on the development of new tools for such studies. The position is available immediately. Applicants are required to submit a resume and copy of their studies record.
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  • I. Karach, A. Botvinik, D. G. Truhlar, W. Wu, A. Shurki, (2017) "Assessing the performance of ab initio classical valence bond methods for hydrogen transfer reactions" Comput. Theor. Chem., 1116:234-241
  • A. Shurki, (2017) "Empirical Valence Bond Simulations of Biological Systems" in Theory and Applications of the Empirical Valence Bond Approach: From Physical Chemistry to Chemical Biology" Eds. F. Duarte, S. C. L. Kamerlin, publisher Wiley, Chap. 6 pp. 145-172 A
  • E. Kozela, C. Haj, L. Hanuš, M. Chourasia, A. Shurki, A. Juknat, N. Kaushansky, R. Mechoulam, Z. Vogel (2016) "HU-446 and HU-465, derivatives of the non-psychoactive cannabinoid cannabidiol, decrease the activation of encephalitogenic T cells" Chemical Biology & Drug Design, 87:143-53
  • A. Sharir-Ivry, R. Varatharaj, A. Shurki, (2015) "Valence Bond and Enzyme Catalysis: A Time to Breakdown and a Time to Buildup", Chem. - Eur. J., 21:7159-7169
  • R. Smoum, S. Baraghithy, M. Chourasia,, A. Breuer, N. Mussai, M. Attar-Namdar, N. Kogan, B. Raphael, D. Bolognini, M. Grazia Cascio, Pietro Marini, R. Pertwee, A. Shurki, R. Mechoulam, I. Bab (2015) "CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: an inverse relationship between binding affinity and biological potency" Proc. Natl. Acad. Sci. U.S.A., 112:8774–8779
  • A. Shurki, E. Derat, A. Barrozo, L. Kamerlin, (2015) "How Valence Bond can help you understand your (bio)chemical reaction?" Chem. Soc. Rev., 44:1037–1052 review article (cover)
  • A. Sharir-Ivry, R. Varatharaj, A. Shurki, (2015) "Challenges within the Linear Response Approximation When Studying Enzyme Catalysis and Effects of Mutations" J. Chem. Theory Comput., 11:293–302
  • A. Shurki, A. Sharir-Ivry, (2014) "Valence-Bond Based Hybrid Quantum Mechanics Molecular Mechanics Approaches and Proper Inclusion of the Effect of the Surrounding", Isr. J. Chem., 54:1189–1204 review article
  • Y. Wolanov, A. Shurki, P. V. Prikhodchenko, T. A. Tripol'skaya, V. V. Novotortsev, R. Pedahzur, O. Lev, (2014) "Aqueous stability of alumina and silica perhydrate hydrogel: Experiments and computations", Dalton Trans., 43:16614-16625 (cover)
  • T. Ansbacher, M. Chourasia, A. Shurki, (2013) "Copper-chaperones with dicoordinated Cu(I) - unique protection mechanism", Proteins: Struct., Funct., Bioinf., 81:1411–1419
  • T. Ansbacher, A. Shurki (2012) "Predicting Coordination Number within Copper Chaperones: Atox1 as Case Study" J. Phys. Chem. B, 116:4425-4432
  • T. Ansbacher, H. K. Srivastava, T. Stein, R. Baer, M. Merkx, A. Shurki (2012) "Calculation of Transition Dipole Moment in Fluorescent Proteins–Towards Efficient Energy Transfer" Phys. Chem. Chem. Phys. 14:4109-4117
  • M. Amitay, A. Shurki, (2011) “Hydrolysis of Organophosphate Compounds by Mutant Butyrylcholinesterase – A Story of Two Histidines” Proteins: Struct. Funct. BioInfo. 79:352-364
  • A. Sharir-Ivry, T. Shnerb, M. Strajbl, A. Shurki (2010) “VB/MM Protein Landscapes: A Study of the SN2 Reaction in Haloalkane Dehalogenase” J. Phys. Chem. B, 114:2212–2218
  • H. K. Srivastava, A. Al A. Al Quntar, A. Azab, M. Srebnik, A. Shurki, (2009) "A Comparison of Amine-Induced Cyclization of 6-Chloro-1-hexynylphosphonate and Isobutyl 7-Chlorohept-2-ynoate", Tetrahedron, 65: 4389-4395
  • M. Amitay, A. Shurki, (2009) “The Structure of G117H Mutant of Butyrylcholinesterase: Nerve Agents Scavenger”, Proteins: Struct. Func. Bioinfo., 77: 370-377
  • T. Ansbacher, H. K. Srivastava, J. M. L. Martin, A. Shurki (2009) “Can DFT methods Correctly and Efficiently Predict the Coordination Number of Copper(I) Complexes? A case Study.”, J. Comput. Chem., 31:75-83
  • A. Sharir-Ivry, A. Shurki (2008) “A VB/MM View of the Identity SN2 Valence Bond State Correlation Diagram in Aqueous Solution” J. Phys. Chem. A, 112: 13157-13163
  • A. Sharir-Ivry, A. Shurki (2008) “VB/MM - The Validity of the Underlying Approximations", J. Phys. Chem. B 112: 12491-12497
  • A. Sharir-Ivry, H. A. Crown, W Wu, A. Shurki (2008) “Density Embedded VB/MM: A Hybrid ab-initio VB/MM with Electrostatic Embedding” J. Phys. Chem. A 112:2489 -2496
  • T. Shnerb, N. Lin, A. Shurki (2007) “What is the Role of the Helical Domain of Gsα in the GTPase Reaction”, Biochem., 46:10875-10885
  • Quntar, H. K. Srivastava, M. Srebnik, A. Melman, R. Ta-Shma A. Shurki (2007) “Formation of Diethyl 2-Amino-1-cyclopentenylphosphonates – Simple Synthesis and Unique Mechanism”, J. Org. Chem. 72:4932-4935
  • A. Shurki, (2006) “Valence Bond – Rebirth of the Phoenix or Relic from the Stone Age” Theor. Chem. Acc., 216:253-261
  • A. Shurki, H. Crown (2005) “Hybrid ab-initio VB/MM method – A Valence Bond Ride through Classical Landscapes” J. Phys Chem. B, 109:23638 – 23644
  • A. Shurki, M. Štrajbl, C. N. Schutz, A. Warshel, (2004). "Electrostatic Basis for Bioenergetics", Methods in Enzymology, 380:52-84
  • A. Shurki, A. Warshel, (2004) “Why does the Ras Switch “Break” By Oncogenic Mutations?” Proteins, 55:1-10
  • A. Shurki, A. Warshel, (2003). “Structure/Function Correlations of Enzymes using MM, QM/MM and Related Approaches; Methods, Concepts, Pitfalls and Current Progress”, Adv. Protein Chem., Vol. 66 Protein Simulations, 249-313
  • M. Štrajbl, A. Shurki, A. Warshel, (2003) “Converting conformational changes to electrostatic energy in molecular motors: The energetics of ATP synthase” P. Nat. Acad. Sci. USA 100:14834-14839
  • M. Štrajbl, A. Shurki, M. Kato, A. Warshel, (2003) “The apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization” J. Am. Chem. Soc. 125:10228-10237
  • A. Shurki, M. Štrajbl, J. Villà, A. Warshel, (2002). “How Much Do Enzymes Really Gain by Restraining Their Reacting Fragments?” J. Am. Chem. Soc. 124:4097-4107
  • A. Shurki, P. C. Hiberty, F. Dijkstra, S. Shaik, (2003). “Aromaticity and Antiaromaticity: What Role Do Ionic Configurations Play in Delocalization and Induction of Magnetic Properties?” J. Phys. Org. Chem. 16:731-745
  • S. Shaik, A. Shurki, D. Danovich, P. C. Hiberty, (2001). "A Different Story of π-Delocalization ― The Distortivity of π-Electrons and Its Chemical Manifestations." Chem. Rev. 101:1501-1540
  • W. Wu, D. Danovich, A. Shurki, S. Shaik, (2000). “Using Valence Bond Theory to Understand Electronic States: Application to the Hidden Excited State (21Ag) of C2nH2n+2 (n=2-14) Polyenes.” J. Phys. Chem. A 104:8744-8758
  • J. M. Galbraith, A. Shurki, S. Shaik, (2000). “A Valence Bond Study of the Bonding in First Row Transition Metal Hydride Cations: What Energetic Role Does Covalency Play?” J. Phys. Chem. A 104:1262-1270
  • A. Shurki, P. C. Hiberty, S. Shaik, (1999). "Charge-Shift Bonding in Group IVB Halides: A Valence Bond Study of MH3-Cl (M=C, Si, Ge, Sn, Pb) Molecules", J. Am. Chem. Soc. 121:822-834
  • S. Shaik, A. Shurki, (1999). "Valence Bond Diagrams and Chemical Reactivity", Angew. Chem. 111:616-657, Angew. Chem. Int. Ed. Engl. 38:586-625
  • A. Shurki, S. Shaik, (1998). "The perfectly resonating state: a chemical model for the transition state", J. Mol. Struct. (THEOCHEM) 424:37-45
  • S. Shaik, A. Shurki, D. Danovich, P. C. Hiberty, (1997). "A Different Story of benzene", Proceedings of the WATOC'96 Conference, July 7-14, 1996, Jerusalem., J. Mol. Struct. (THEOCHEM) 398-399:155-167
  • A. Shurki, S. Shaik, (1997). "The Distortive Tendency of Benzene π electrons: How is it Related to Structural Observations?", Angew. Chem. 109:2322-2324, Angew. Chem. Int. Ed. Engl. 36:2205-2208 (Reviewed in C&E News, Nov 3, 1997, in "Science/Technology Concentrates")
  • S. Shaik, A. Shurki, D. Danovich, P. C. Hiberty, (1996). "Origins of the exalted b2u frequency in the first exited state of benzene", J. Am. Chem. Soc. 118:666-671
  • P. C. Hiberty, D. Danovich, A. Shurki, S. Shaik, (1995). "Why does benzene possess a D6h symmetry? A quasiclassical state approach for probing π-bonding and delocalization energies", J. Am. Chem. Soc. 117:7760-7768
  • N. Muskal, I. Turyan, A. Shurki, D. Mandler, (1995). "Chiral Self-Assembled Monolayers", J. Am. Chem. Soc., 117:1147-1148
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