Ran Friedman

I am a professor of chemistry with focus on computational chemistry and biochemistry. I teach medicinal and physical chemistry in various courses. I carry out research within the field of computational chemistry, which means that I study chemistry with the help of computer simulations and modelling.

Teaching

I am teaching chemistry mainly to students of nutritional sciences and pharmacy. I teach physical chemistry for the first group and medicinal chemistry for the second. I am also involved at teaching M.Sc and Ph.D students at time.

Research

My research focuses on computational chemistry with specialisation on biomolecules. I want to deepen the understanding of the molecular aspects of diseases through modelling and simulation. In addition, I have interest in protein-ion Interactions. In my research group, we use molecular dynamics simulations, quantum chemistry, and stochastic modelling.

My research groups

My ongoing research projects

Project: Understanding and controlling resistance mutations in leukaemias The long term objective of this project is to reduce the risk for resistance to targeted therapies in cancers. Our theory is…

Publications

Article in journal (Refereed)

Lindström, H.J.G., De Wijn, A.S., Friedman, R. (2024). Interplay of mutations, alternate mechanisms, and treatment breaks in leukaemia : Understanding and implications studied with stochastic models. Computers in Biology and Medicine. 169.
Status: Published
Freire, T.S., Zukerman-Schpector, J., Friedman, R., Caracelli, I. (2024). Structural and thermodynamic characterization of allosteric transitions in human serum albumin with metadynamics simulations. Physical Chemistry, Chemical Physics - PCCP. 26 (7). 6436-6447.
Status: Published
Yang, J., Friedman, R. (2024). Synergy and antagonism between azacitidine and FLT3 inhibitors. Computers in Biology and Medicine. 169. 107889-107889.
Status: Published
Freire, T.S., Caracelli, I., Zukerman-Schpector, J., Friedman, R. (2023). Resistance to a tyrosine kinase inhibitor mediated by changes to the conformation space of the kinase. Physical Chemistry, Chemical Physics - PCCP. 25 (8). 6175-6183.
Status: Published
Friedman, R. (2023). Estimating the Gibbs Hydration Energies of Actinium and Trans-Plutonium Actinides. ChemPhysChem. 24 (2).
Status: Published
Meelua, W., Wanjai, T., Thinkumrob, N., Friedman, R., Jitonnom, J. (2023). Multiscale QM/MM Simulations Identify the Roles of Asp239 and 1‑OH···Nucleophile in Transition State Stabilization in Arabidopsis thaliana Cell-Wall Invertase 1. Journal of Chemical Information and Modeling. 63 (15). 4827-4838.
Status: Published
Månsson, A., Ušaj, M., Moretto, L., Matusovsky, O., Velayuthan, L.P., et al. (2023). New paradigms in actomyosin energy transduction : Critical evaluation of non-traditional models for orthophosphate release. Bioessays. 45 (9).
Status: Published
Yang, J., Friedman, R. (2023). Combination strategies to overcome drug resistance in FLT+ acute myeloid leukaemia. Cancer Cell International. 23 (1).
Status: Published
Oruganti, B., Lindahl, E., Yang, J., Amiri, W., Rahimullah, R., et al. (2022). Allosteric enhancement of the BCR-Abl1 kinase inhibition activity of nilotinib by cobinding of asciminib. Journal of Biological Chemistry. 298 (8).
Status: Published
Lindström, J., Friedman, R. (2022). Rotating between ponatiniband imatinib temporarily increasesthe efficacy of imatinib as shownin a chronic myeloid leukaemiamodel. Scientific Reports. 12.
Status: Published
Xu, Y., Zhang, S., Lindahl, E., Friedman, R., Wu, W., et al. (2022). A general tight-binding based energy decomposition analysis scheme for intermolecular interactions in large molecules. Journal of Chemical Physics. 157 (3).
Status: Published
Friedman, R. (2022). Computational studies of protein–drug binding affinity changes upon mutations in the drug target. Wiley Interdisciplinary Reviews. Computational Molecular Science. 12 (1).
Status: Published
Friedman, R. (2022). The molecular mechanisms behind activation of FLT3 in acute myeloid leukemia and resistance to therapy by selective inhibitors. Biochimica et Biophysica Acta. CR. Reviews on Cancer. 1877 (1).
Status: Published
Moretto, L., Ušaj, M., Matusovsky, O., Rassier, D.E., Friedman, R., et al. (2022). Multistep orthophosphate release tunes actomyosin energy transduction. Nature Communications. 13 (1).
Status: Published
Xu, Y., Friedman, R., Wu, W., Su, P. (2021). Understanding intermolecular interactions of large systems in ground state and excited state by using density functional based tight binding methods. Journal of Chemical Physics. 154 (19).
Status: Published
Oruganti, B., Friedman, R. (2021). Activation of Abl1 Kinase Explored Using Well-Tempered Metadynamics Simulations on an Essential Dynamics Sampled Path. Journal of Chemical Theory and Computation. 17 (11). 7260-7270.
Status: Published
Yang, J., Lindström, J., Friedman, R. (2021). Combating drug resistance in acute myeloid leukaemia by drug rotations : the effects of quizartinib and pexidartinib. Cancer Cell International. 21 (1).
Status: Published
Friedman, R. (2021). Preferential Binding of Lanthanides to Methanol Dehydrogenase Evaluated with Density Functional Theory. Journal of Physical Chemistry B. 125 (9). 2251-2257.
Status: Published
Houshmand, F., Friedman, R., Jalili, S., Schofield, J. (2020). Exciton effect in new generation of carbon nanotubes : graphdiyne nanotubes. Journal of Molecular Modeling. 26 (7). 1-10.
Status: Published
Lindström, J., Friedman, R. (2020). Inferring time-dependent population growth rates in cell cultures undergoing adaptation. BMC Bioinformatics. 21 (1). 1-13.
Status: Published
Lindström, J., Friedman, R. (2020). The effects of combination treatments on drug resistance in chronic myeloid leukaemia : an evaluation of the tyrosine kinase inhibitors axitinib and asciminib. BMC Cancer. 20 (1).
Status: Published
Todde, G., Friedman, R. (2020). Pattern and Dynamics of FLT3 Duplications. Journal of Chemical Information and Modeling. 60 (8). 4005-4020.
Status: Published
Buetti-Dinh, A., Herold, M., Christel, S., El Hajjami, M., Delogu, F., et al. (2020). Reverse engineering directed gene regulatory networks from transcriptomics and proteomics data of biomining bacterial communities with approximate Bayesian computation and steady-state signalling simulations. BMC Bioinformatics. 21 (1). 1-15.
Status: Published
Georgoulia, P.S., Bjelic, S., Friedman, R. (2020). Deciphering the molecular mechanism of FLT3 resistance mutations. The FEBS Journal. 287 (15). 3200-3220.
Status: Published
Davila-Rodriguez, M.J., Freire, T.S., Lindahl, E., Caracelli, I., Zukerman-Schpector, J., et al. (2020). Is breaking of a hydrogen bond enough to lead to drug resistance?. Chemical Communications. 56 (49). 6727-6730.
Status: Published
Lindström, J., De Wijn, A.S., Friedman, R. (2019). Stochastic modelling of tyrosine kinase inhibitor rotation therapy in chronic myeloid leukaemia. BMC Cancer. 19. 1-13.
Status: Published
Todde, G., Friedman, R. (2019). Activation and Inactivation of the FLT3 Kinase: Pathway Intermediates and the Free Energy of Transition. Journal of Physical Chemistry B. 123 (26). 5385-5394.
Status: Published
Georgoulia, P.S., Todde, G., Bjelic, S., Friedman, R. (2019). The catalytic activity of Abl1 single and compound mutations : Implications for the mechanism of drug resistance mutations in chronic myeloid leukaemia. Biochimica et Biophysica Acta - General Subjects. 1863 (4). 732-741.
Status: Published
Steinz, M.M., Persson, M., Aresh, B., Olsson, K., Cheng, A.J., et al. (2019). Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis. JCI Insight. 4 (9). 1-16.
Status: Published
Friedman, R. (2019). Specific Ion and Concentration Effects in Acetate Solutions with Na+, K+ and Cs+. ChemPhysChem. 20 (8). 1006-1010.
Status: Published
Todde, G., Friedman, R. (2019). Conformational modifications induced by internal tandem duplications on the FLT3 kinase and juxtamembrane domains. Physical Chemistry, Chemical Physics - PCCP. 21 (34). 18467-18476.
Status: Published
Gagner, V.A., Lundholm, I., Garcia-Bonete, M., Rodilla, H., Friedman, R., et al. (2019). Clustering of atomic displacement parameters in bovine trypsin reveals a distributed lattice of atoms with shared chemical properties. Scientific Reports. 9. 1-14.
Status: Published
Friedman, R. (2019). Simulations of Biomolecules in Electrolyte Solutions. Advanced Theory and Simulations. 2 (4). 1-10.
Status: Published
Buetti-Dinh, A., Friedman, R. (2018). Computer simulations of the signalling network in FLT3⁺-acute myeloid leukaemia : indications for an optimal dosage of inhibitors against FLT3 and CDK6. BMC Bioinformatics. 19. 1-13.
Status: Published
Friedman, R. (2018). Membrane-Ion Interactions. Journal of Membrane Biology. 251 (3). 453-460.
Status: Published
Ahlstrand, E., Buetti-Dinh, A., Friedman, R. (2018). An interactive computer lab of the galvanic cell for students in biochemistry. Biochemistry and molecular biology education. 46 (1). 58-65.
Status: Published
Buetti-Dinh, A., Jensen, R., Friedman, R. (2018). A computational study of hedgehog signalling involved in basal cell carcinoma reveals the potential and limitation of combination therapy. BMC Cancer. 18 (1). 1-8.
Status: Published
Friedman, R. (2017). The molecular mechanism behind resistance of the kinase FLT3 to the inhibitor quizartinib. Proteins : Structure, Function, and Bioinformatics. 85 (11). 2143-2152.
Status: Published
Ahlstrand, E., Hermansson, K., Friedman, R. (2017). Interaction Energies in Complexes of Zn and Amino Acids : A Comparison of Ab Initio and Force Field Based Calculations. Journal of Physical Chemistry A. 121 (13). 2643-2654.
Status: Published
Karlsson, B.C.G., Friedman, R. (2017). Dilution of whisky - the molecular perspective. Scientific Reports. 7 (6489).
Status: Published
Ahlstrand, E., Zukerman Schpector, J., Friedman, R. (2017). Computer simulations of alkali-acetate solutions : Accuracy of the forcefields in difference concentrations. Journal of Chemical Physics. 147. 1-10.
Status: Published
Becconi, O., Ahlstrand, E., Salis, A., Friedman, R. (2017). Protein-ion Interactions : Simulations of Bovine Serum Albumin in Physiological Solutions of NaCl, KCl and LiCl. Israel Journal of Chemistry. 57 (5). 403-412.
Status: Published
Maganhi, S.H., Jensen, P., Caracelli, I., Schpector, J.Z., Froehling, S., et al. (2017). Palbociclib can overcome mutations in cyclin dependent kinase 6 that break hydrogen bonds between the drug and the protein. Protein Science. 26 (4). 870-879.
Status: Published
Pineda De Castro, L.F., Dopson, M., Friedman, R. (2016). Biological Membranes in Extreme Conditions : Anionic Tetraether Lipid Membranes and Their Interactions with Sodium and Potassium. Journal of Physical Chemistry B. 120 (41). 10628-10634.
Status: Published
Buetti-Dinh, A., O'hare, T., Friedman, R. (2016). Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy. PLOS ONE. 11 (9).
Status: Published
Friedman, R. (2016). Drug resistance in cancer : molecular evolution and compensatory proliferation. Oncotarget. 7 (11). 11746-11755.
Status: Published
Buetti-Dinh, A., Dethlefsen, O., Friedman, R., Dopson, M. (2016). Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes. Microbiology. 162 (8). 1422-1434.
Status: Published
Pineda De Castro, L.F., Dopson, M., Friedman, R. (2016). Biological Membranes in Extreme Conditions : Simulations of Anionic Archaeal Tetraether Lipid Membranes. PLOS ONE. 11 (5).
Status: Published
Lundholm, I.V., Rodilla, H., Wahlgren, W.Y., Duelli, A., Bourenkov, G., et al. (2015). Terahertz radiation induces non-thermal structural changes associated with Fröhlich condensation in a protein crystal. Structural Dynamics. 2 (5).
Status: Published
Cournia, Z., Allen, T.W., Andricioaei, I., Antonny, B., Baum, D., et al. (2015). Membrane Protein Structure, Function, and Dynamics : a Perspective from Experiments and Theory. Journal of Membrane Biology. 248 (4). 611-640.
Status: Published
Buetti-Dinh, A., Pivkin, I., Friedman, R. (2015). S100A4 and its role in metastasis – computational integration of data on biological networks. Molecular Biosystems. 11. 2238-2246.
Status: Published
Chavan, S., Friedman, R., Nicholls, I.A. (2015). Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy. International Journal of Molecular Sciences. 16 (5). 11659-11677.
Status: Published
Buetti-Dinh, A., Pivkin, I.V., Friedman, R. (2015). S100A4 and its role in metastasis : simulations of knockout and amplification of epithelial growth factor receptor and matrix metalloproteinases. Molecular Biosystems. 11 (8). 2247-2254.
Status: Published
Friedman, R. (2014). Structural and computational insights into the versatility of cadmium binding to proteins. Dalton Transactions. 43 (7). 2878-2887.
Status: Published
Friedman, R., Caflisch, A. (2014). Wild type and mutants of the HET-s(218-289) prion show different flexibility at fibrillar ends : A simulation study. Proteins : Structure, Function, and Bioinformatics. 82 (3). 399-404.
Status: Published
Zabriskie, M.S., Eide, C.A., Tantravahi, S.K., Vellore, N.A., Estrada, J., et al. (2014). BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia. Cancer Cell. 26 (3). 428-442.
Status: Published
Friedman, R. (2013). Drug Resistance Missense Mutations in Cancer Are Subject to Evolutionary Constraints. PLOS ONE. 8 (12).
Status: Published
Friedman, R. (2013). Electrolyte Solutions and Specific Ion Effects on Interfaces. Journal of Chemical Education. 90 (8). 1018-1023.
Status: Published
Karlsson, B.C.G., Olsson, G.D., Friedman, R., Rosengren, A.M., Henschel, H., et al. (2013). How warfarin’s structural diversity influences its phospholipid bilayer membrane permeation. Journal of Physical Chemistry B. 117 (8). 2384-2395.
Status: Published
Ahlstrand, E., Spångberg, D., Hermansson, K., Friedman, R. (2013). Interaction energies between metal ions (Zn²⁺ and Cd²⁺) and biologically relevant ligands. International Journal of Quantum Chemistry. 113 (23). 2554-2562.
Status: Published
Friedman, R. (2011). Aggregation of amyloids in a cellular context : modelling and experiment. Biochemical Journal. 438. 415-426.
Status: Published
Friedman, R., Caflisch, A. (2011). Surfactant Effects on Amyloid Aggregation Kinetics. Journal of Molecular Biology. 414. 303-312.
Status: Published
Friedman, R. (2011). Ions and the protein surface revisited : extensive molecular dynamics simulations and analysis of protein structures in alkali-chloride solutions. Journal of Physical Chemistry B. 115. 9213-9223.
Status: Published
Seeber, M., Felline, A., Raimondi, F., Muff, S., Friedman, R., et al. (2011). Wordom : a user-friendly program for the analysis of molecular conformations, trajectories, and free energy surfaces. Journal of Computational Chemistry. 32 (6). 1183-1194.
Status: Published
Friedman, R., Pellarin, R., Caflisch, A. (2010). Soluble Protofibrils as Metastable Intermediates in Simulations of Amyloid Fibril Degradation Induced by Lipid Vesicles. Journal of Physical Chemistry Letters. 1 (2). 471-474.
Status: Published
Friedman, R., Caflisch, A. (2010). On the orientation of the catalytic dyad in aspartic proteases. Proteins : Structure, Function, and Bioinformatics. 78 (6). 1575-1582.
Status: Published
Friedman, R., Caflisch, A. (2009). Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring. ChemMedChem. 4 (8). 1317-1326.
Status: Published
Friedman, R., Pellarin, R., Caflisch, A. (2009). Amyloid aggregation on lipid bilayers and its impact on membrane permeability. Journal of Molecular Biology. 387 (2). 407-415.
Status: Published
Friedman, R. (2009). Proton Transfer on the Molecular Surface of Proteins and Model Systems. Israel Journal of Chemistry. 49 (2). 149-153.
Status: Published
Dashevskaya, S., Kopito, R.B., Friedman, R., Elbaum, M., Epel, B.L. (2008). Diffusion of anionic and neutral GFP derivatives through plasmodesmata in epidermal cells of Nicotiana benthamiana. Protoplasma.
Status: Published
Friedman, R., Caflisch, A. (2008). Pepsinogen-like activation intermediate of plasmepsin II revealed by molecular dynamics analysis. Proteins : Structure, Function, and Bioinformatics. 73 (4). 814-827.
Status: Published
Friedman, R., Fischer, S., Nachliel, E., Scheiner, S., Gutman, M. (2007). Minimum energy pathways for proton transfer between adjacent sites exposed to water. Journal of Physical Chemistry B. 111 (21). 6059-6070.
Status: Published
Tsfadia, Y., Friedman, R., Kadmon, J., Selzer, A., Nachliel, E., et al. (2007). Molecular dynamics simulations of palmitate entry into the hydrophobic pocket of the fatty acid binding protein. FEBS Letters. 581. 1243-1247.
Status: Published
Friedman, R. (2007). Myosin V movement : Lessons from molecular dynamics studies of IQ peptides in the lever arm. Biochemistry. 46 (50). 14524-14536.
Status: Published
Friedman, R., Caflisch, A. (2007). The Protonation State of the Catalytic Aspartates in Plasmepsin II. FEBS Letters. 581. 4120-4124.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2006). Fatty Acid Binding Proteins - Same Structure but Different Binding Mechanisms? : Molecular Dynamics Simulations of Intestinal Fatty Acid Binding Protein. Biophysical Journal. 90. 1535-45.
Status: Published
Gutman, M., Nachliel, E., Friedman, R. (2006). The dynamics of proton transfer between adjacent sites. Photochemical and Photobiological Sciences. 5. 531-537.
Status: Published
Ganoth, A., Friedman, R., Nachliel, E., Gutman, M. (2006). A molecular dynamics study and free energy analysis of complexes between the Mlc1p protein and two IQ motif peptides. Biophysical Journal. 91 (7). 2436-2450.
Status: Published
Project, E., Friedman, R., Nachliel, E., Gutman, M. (2006). A Molecular Dynamics Study of the Effect of Ca²⁺ Removal on Calmodulin Structure. Biophys. J.. 90. 3842-3850.
Status: Published
Ganoth, A., Nachliel, E., Friedman, R., Gutman, M. (2006). Molecular dynamics study of a calmodulin-like protein with an IQ peptide : spontaneous refolding of the protein around the peptide. Proteins : Structure, Function, and Bioinformatics. 64 (1). 133-146.
Status: Published
Gutman, M., Nachliel, E., Friedman, R. (2006). The mechanism of proton transfer between adjacent sites on the molecular surface. Biochimica et Biophysica Acta. 1757. 931-941.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2005). Molecular Dynamics of a Protein Surface : Ion-Residues Interactions. Biophysical Journal. 89 (2). 768-781.
Status: Published
Mezer, A., Friedman, R., Noivirt, O., Nachliel, E., Gutman, M. (2005). The mechanism of proton transfer between adjacent sites exposed to water. J. Chem. Phys. B. 109. 11379-11388.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2005). Protein surface dynamics : Interaction with water and small solutes. Journal of biological physics (Print). 31 (3). 433-452.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2005). Application of Classical Molecular Dynamics for Evaluation of Proton Transfer Mechanism on a Protein. Bioch. Bioph. Acta.. 1710. 67-77.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2005). Molecular Dynamics Simulations of the Adipocyte Lipid Binding Protein Reveal a Novel Entry Site for the Ligand. Biochemistry. 44. 4275-4283.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2005). Protein Surface - the Dynamics of the Interactions between Protein, Water and Small Solutes. Journal of biological physics (Print). 31 (3-4). 433-452.
Status: Published
Friedman, R., Nachliel, E., Gutman, M. (2003). The role of small intraprotein cavities in the catalytic cycle of bacteriorhodopsin. Biophysical Journal. 85 (2). 886-896.
Status: Published

Conference paper (Refereed)

Steinz, M., Malin, P., Bejan, A., Cheng, A., Ahlstrand, E., et al. (2018). Identification of oxidative hotspots on actin which promote skeletal muscle weakness in rheumatoid arthritis. Free Radical Biology and Medicine. S106.
Katona, G., Lundholm, I., Rodilla, H., Garcia-Bonete, M., Duelli, A., et al. (2016). Bayesian analysis of non-thermal structural changes induced by terahertz radiation in protein crystals. 2016 41ST INTERNATIONAL CONFERENCE ON INFRARED, MILLIMETER, AND TERAHERTZ WAVES (IRMMW-THZ).

Chapter in book (Refereed)

Friedman, R. (2024). The Emerging Role of Molecular Dynamics Simulations in Cancer Research. Comprehensive Computational Chemistry : Molecular Dynamics Simulations and Reaction Rates. Oxford. UK, Elsevier. 910-920.

Article, review/survey (Refereed)

Friedman, R., Bjelic, S. (2020). Simulations Studies of Protein Kinases that are Molecular Targets in Cancer. Israel Journal of Chemistry. John Wiley & Sons. 60 (7). 667-680.
Status: Published
Friedman, R., Khalid, S., Aponte-Santamaria, C., Arutyunova, E., Becker, M., et al. (2018). Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology. Journal of Membrane Biology. Springer. 251 (5-6). 609-631.
Status: Published
Friedman, R., Boye, K., Flatmark, K. (2013). Molecular modelling and simulations in cancer research. Biochimica et Biophysica Acta. CR. Reviews on Cancer. 1836 (1). 1-14.
Status: Published

Article in journal (Other academic)

Friedman, R., Agmon, N. (2017). Charge Transfer in Proteins : In Celebration of Hemi Gutman's 80th Birthday. Israel Journal of Chemistry. 57 (5). 355-356.
Status: Published

Manuscript (preprint) (Other academic)

Lindström, J., De Wijn, A.S., Friedman, R. Modelling resistance in leukaemia mediated by mutations and alternate mechanisms – their interactions and treatment-free periods (drug holidays)..
Lindström, J., Friedman, R. Inferring time-dependent growth rates in cell cultures undergoing adaptation.