A Warshel

Summary

Affiliation: University of Southern California
Country: USA

Publications

  1. doi request reprint Simulating electrostatic energies in proteins: perspectives and some recent studies of pKas, redox, and other crucial functional properties
    Arieh Warshel
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 79:3469-84. 2011
  2. pmc Inverting the selectivity of aquaporin 6: gating versus direct electrostatic interaction
    Arieh Warshel
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 102:1813-4. 2005
  3. pmc Exploring the role of large conformational changes in the fidelity of DNA polymerase beta
    Yun Xiang
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Proteins 70:231-47. 2008
  4. ncbi request reprint Modeling electrostatic effects in proteins
    Arieh Warshel
    University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Biochim Biophys Acta 1764:1647-76. 2006
  5. ncbi request reprint Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase
    Arieh Warshel
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 46:1466-76. 2007
  6. ncbi request reprint Electrostatic basis for enzyme catalysis
    Arieh Warshel
    Department of Chemistry, University of Southern California, SGM Building 418, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Chem Rev 106:3210-35. 2006
  7. ncbi request reprint Protein control of iron-sulfur cluster redox potentials
    R Langen
    Department of Chemistry, University of Southern California, Los Angeles 90089 0482
    J Biol Chem 267:25625-7. 1992
  8. doi request reprint Quantifying free energy profiles of proton transfer reactions in solution and proteins by using a diabatic FDFT mapping
    Yun Xiang
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 112:1007-15. 2008
  9. pmc Computer simulations of protein functions: searching for the molecular origin of the replication fidelity of DNA polymerases
    Jan Florian
    Department of Chemistry, Loyola University, Chicago, IL 60626, USA
    Proc Natl Acad Sci U S A 102:6819-24. 2005
  10. pmc The empirical valence bond as an effective strategy for computer-aided enzyme design
    Alexandra Vardi-Kilshtain
    Department of Chemistry, University of Southern California, Los Angeles, USA
    Biotechnol J 4:495-500. 2009

Research Grants

  1. Computer Simulation of Electron and Proton Transfer
    Arieh Warshel; Fiscal Year: 2010
  2. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2001
  3. COMPUTER SIMULATION OF ELECTRON TRANSFER REACTIONS
    Arieh Warshel; Fiscal Year: 2000
  4. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2010
  5. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2009
  6. Computer Simulation of Electron and Proton Transfer
    Arieh Warshel; Fiscal Year: 2007
  7. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2007
  8. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2006
  9. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2005
  10. Computer Simulation of Electron and Proton Transfer
    Arieh Warshel; Fiscal Year: 2004

Collaborators

Detail Information

Publications83

  1. doi request reprint Simulating electrostatic energies in proteins: perspectives and some recent studies of pKas, redox, and other crucial functional properties
    Arieh Warshel
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 79:3469-84. 2011
    ..We also emphasize recent advances in coarse grained models with a physically based electrostatic treatment and provide some examples including further directions in treating voltage activated ion channels...
  2. pmc Inverting the selectivity of aquaporin 6: gating versus direct electrostatic interaction
    Arieh Warshel
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 102:1813-4. 2005
  3. pmc Exploring the role of large conformational changes in the fidelity of DNA polymerase beta
    Yun Xiang
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Proteins 70:231-47. 2008
    ..The generation of free energy surfaces for R and W also allow us to analyze proposals about the relationship between induced fit and fidelity...
  4. ncbi request reprint Modeling electrostatic effects in proteins
    Arieh Warshel
    University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Biochim Biophys Acta 1764:1647-76. 2006
    ....
  5. ncbi request reprint Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase
    Arieh Warshel
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 46:1466-76. 2007
    ..It seems to us that this work provides an excellent example of the need for computational studies in analyzing key experimental findings about enzyme catalysis...
  6. ncbi request reprint Electrostatic basis for enzyme catalysis
    Arieh Warshel
    Department of Chemistry, University of Southern California, SGM Building 418, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Chem Rev 106:3210-35. 2006
  7. ncbi request reprint Protein control of iron-sulfur cluster redox potentials
    R Langen
    Department of Chemistry, University of Southern California, Los Angeles 90089 0482
    J Biol Chem 267:25625-7. 1992
    ..Our calculations provide the first successful quantitative modeling of the protein control of iron-sulfur cluster redox potentials...
  8. doi request reprint Quantifying free energy profiles of proton transfer reactions in solution and proteins by using a diabatic FDFT mapping
    Yun Xiang
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 112:1007-15. 2008
    ..Our results point out that the present implementation of the FDFT approach provides a very promising approach for evaluating QM(ai)/MM free energy surfaces...
  9. pmc Computer simulations of protein functions: searching for the molecular origin of the replication fidelity of DNA polymerases
    Jan Florian
    Department of Chemistry, Loyola University, Chicago, IL 60626, USA
    Proc Natl Acad Sci U S A 102:6819-24. 2005
    ..The calculations demonstrate the potential for further integration of theoretical and experimental studies to analyze high- and low-fidelity DNA polymerases...
  10. pmc The empirical valence bond as an effective strategy for computer-aided enzyme design
    Alexandra Vardi-Kilshtain
    Department of Chemistry, University of Southern California, Los Angeles, USA
    Biotechnol J 4:495-500. 2009
    ..The ability of the model to predict quantitatively the catalytic power of enzymes should augment the capacity of current approaches for enzyme design...
  11. ncbi request reprint Structure/function correlations of proteins using MM, QM/MM, and related approaches: methods, concepts, pitfalls, and current progress
    A Shurki
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Adv Protein Chem 66:249-313. 2003
  12. ncbi request reprint Origin of the temperature dependence of isotope effects in enzymatic reactions: the case of dihydrofolate reductase
    Hanbin Liu
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 111:7852-61. 2007
    ....
  13. pmc Studies of proton translocations in biological systems: simulating proton transport in carbonic anhydrase by EVB-based models
    Sonja Braun-Sand
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Biophys J 87:2221-39. 2004
    ....
  14. ncbi request reprint The catalytic effect of dihydrofolate reductase and its mutants is determined by reorganization energies
    Hanbin Liu
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 46:6011-25. 2007
    ..Thus, as far as catalysis is concerned, the change in the activation barrier is due to the change in the electrostatic preorganization energy...
  15. ncbi request reprint On the origin of the electrostatic barrier for proton transport in aquaporin
    Anton Burykin
    Department of Chemistry, University of Southern California, 3620 McClintock Ave SGM 418, Los Angeles, CA 90089 1062, USA
    FEBS Lett 570:41-6. 2004
    ..Using this definition and "mutating" the NPA residues to their non-polar analogues establishes that these residues do not provide the major contribution to the solvation barrier...
  16. pmc Transition state theory can be used in studies of enzyme catalysis: lessons from simulations of tunnelling and dynamical effects in lipoxygenase and other systems
    Mats H M Olsson
    Department of Chemistry, University of Southern California, 3620 South McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Philos Trans R Soc Lond B Biol Sci 361:1417-32. 2006
    ....
  17. ncbi request reprint Modifying the beta,gamma leaving-group bridging oxygen alters nucleotide incorporation efficiency, fidelity, and the catalytic mechanism of DNA polymerase beta
    Christopher A Sucato
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Biochemistry 46:461-71. 2007
    ..The results are addressed theoretically in terms of the energetics of successive primer 3'-O addition (bond forming) and pyrophosphate analogue elimination (bond breaking) reaction energy barriers...
  18. ncbi request reprint How much do enzymes really gain by restraining their reacting fragments?
    A Shurki
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    J Am Chem Soc 124:4097-107. 2002
    ..This solvent-induced effect is quite different from the traditional picture of balance between the repulsive interaction of the reactive fragments and the steric force of the protein...
  19. pmc DNA polymerase beta catalytic efficiency mirrors the Asn279-dCTP H-bonding strength
    Vaclav Martinek
    Department of Chemistry, Loyola University Chicago, Chicago, IL 60626, USA
    FEBS Lett 581:775-80. 2007
    ..This finding is consistent with the view that enzyme preorganization plays a major role in controlling DNA polymerase specific activity...
  20. ncbi request reprint DNA polymerase beta fidelity: halomethylene-modified leaving groups in pre-steady-state kinetic analysis reveal differences at the chemical transition state
    Christopher A Sucato
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Biochemistry 47:870-9. 2008
    ..Solvent pH and deuterium isotope-effect data are also used to evaluate mechanistic differences between correct and mispaired incorporation...
  21. ncbi request reprint Predicting drug-resistant mutations of HIV protease
    Hiroshi Ishikita
    Department of Chemistry, University of Southern California, 418 SGM Building, Los Angeles, CA 90089, USA
    Angew Chem Int Ed Engl 47:697-700. 2008
  22. ncbi request reprint What are the dielectric "constants" of proteins and how to validate electrostatic models?
    C N Schutz
    Department of Chemistry, University of Southern California, Los Angeles, California, USA
    Proteins 44:400-17. 2001
    ..These include the effect of water penetration and the effect of the protein reorganization. Finally, we show that the optimal dielectric constant for self-energies is not the optimal constant for charge-charge interactions...
  23. ncbi request reprint The barrier for proton transport in aquaporins as a challenge for electrostatic models: the role of protein relaxation in mutational calculations
    Mitsunori Kato
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 64:829-44. 2006
    ..Such calculations also help to clarify the crucial role of solvation energies in establishing the barrier in aquaporins...
  24. doi request reprint Effective approach for calculations of absolute stability of proteins using focused dielectric constants
    Spyridon Vicatos
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Proteins 77:670-84. 2009
    ..8 kcal/mole compared to the observed values, making our method very promising for estimating protein stability. It also provides valuable insight into the complex electrostatic phenomena taking place in folded proteins...
  25. pmc Enzyme millisecond conformational dynamics do not catalyze the chemical step
    Andrei V Pisliakov
    Department of Chemistry SGM 418, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089, USA
    Proc Natl Acad Sci U S A 106:17359-64. 2009
    ..Nevertheless, the precise nature of this coupling is a question of great importance...
  26. pmc What really prevents proton transport through aquaporin? Charge self-energy versus proton wire proposals
    Anton Burykin
    Department of Chemistry, University of Southern California, Los Angeles, California, USA
    Biophys J 85:3696-706. 2003
    ..However, in cases of biological channels, the actual PT mechanism is much less important than the energetics of transferring the proton charge from water to different regions in the channels...
  27. pmc On possible pitfalls in ab initio quantum mechanics/molecular mechanics minimization approaches for studies of enzymatic reactions
    Marco Klahn
    Department of Chemistry, University of Southern California, 3620 South McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 109:15645-50. 2005
    ..The possible relevance of our conclusion with regard to a recent study of the RasGAP reaction is discussed...
  28. pmc On the origin of the catalytic power of carboxypeptidase A and other metalloenzymes
    Alexandra Vardi Kilshtain
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 77:536-50. 2009
    ..This and earlier studies show that the catalytic effect of the metal is not some constant electrostatic effect, that can be assessed from gas phase studies, but a reflection of the dielectric effect of the specific environment...
  29. doi request reprint Dineopentyl phosphate hydrolysis: evidence for stepwise water attack
    Shina C L Kamerlin
    Department of Chemistry, SGM 418, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089, USA
    J Org Chem 73:6960-9. 2008
    ..Our data show that the substrate-as-base mechanism is viable for phosphate ester hydrolysis, which may have important implications for the studies of phosphate ester hydrolysis by enzymes...
  30. pmc On catalytic preorganization in oxyanion holes: highlighting the problems with the gas-phase modeling of oxyanion holes and illustrating the need for complete enzyme models
    Shina C L Kamerlin
    Department of Chemistry SGM418, University of Southern California, 3620 McClintock Avenue, Los Angeles California 90089, USA
    J Org Chem 75:6391-401. 2010
    ..Simply calculating interaction energies with relatively fixed species cannot capture this crucial point, and considering it may help in advancing rational enzyme design...
  31. pmc Examining the case for the effect of barrier compression on tunneling, vibrationally enhanced catalysis, catalytic entropy and related issues
    Shina Caroline Lynn Kamerlin
    Department of Chemistry SGM418, University of Southern California, Los Angeles, CA 90089, USA
    FEBS Lett 584:2759-66. 2010
    ..Finally, the temperature dependence of the entropy change in hydride transfer reactions is shown to reflect simple electrostatic effects...
  32. pmc Magnesium-cationic dummy atom molecules enhance representation of DNA polymerase beta in molecular dynamics simulations: improved accuracy in studies of structural features and mutational effects
    Peter Oelschlaeger
    University of Southern California, Department of Chemistry, Los Angeles, CA 90089 1062, USA
    J Mol Biol 366:687-701. 2007
    ..The model should also have broad applicability to the modeling of other magnesium-containing proteins...
  33. doi request reprint Coarse-grained (multiscale) simulations in studies of biophysical and chemical systems
    Shina C L Kamerlin
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Annu Rev Phys Chem 62:41-64. 2011
    ....
  34. pmc Electrostatic basis for the unidirectionality of the primary proton transfer in cytochrome c oxidase
    Andrei V Pisliakov
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 105:7726-31. 2008
    ....
  35. pmc Exploring pathways and barriers for coupled ET/PT in cytochrome c oxidase: a general framework for examining energetics and mechanistic alternatives
    Mats H M Olsson
    University of Southern California, 3620 McClintock Avenue, Department of Chemistry, SGM 418, Los Angeles, CA 90089 1062, USA
    Biochim Biophys Acta 1767:244-60. 2007
    ....
  36. ncbi request reprint Electrostatic contributions to protein stability and folding energy
    Maite Roca
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    FEBS Lett 581:2065-71. 2007
    ..Although this description should be examined by further microscopic studies, the practical use of the current approach seems to offer a powerful tool for protein design and for studies of the energetics of protein folding...
  37. pmc Multiscale simulations of protein landscapes: using coarse-grained models as reference potentials to full explicit models
    Benjamin M Messer
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 78:1212-27. 2010
    ..Furthermore, the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins is discussed...
  38. pmc On the relationship between thermal stability and catalytic power of enzymes
    Maite Roca
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 46:15076-88. 2007
    ..Thus, the optimized catalysts are less stable. This trend is clearly observed in the DHFR case...
  39. doi request reprint Are mixed explicit/implicit solvation models reliable for studying phosphate hydrolysis? A comparative study of continuum, explicit and mixed solvation models
    Shina C L Kamerlin
    Department of Chemistry, University of Southern California, 3620 McClintock Ave, Los Angeles, CA 90089, USA
    Chemphyschem 10:1125-34. 2009
    ..Thus, our analysis indicates that this approach provides an unreliable way for modelling phosphate hydrolysis in solution...
  40. pmc On the relationship between folding and chemical landscapes in enzyme catalysis
    Maite Roca
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA, 90089 1062, USA
    Proc Natl Acad Sci U S A 105:13877-82. 2008
    ..This work provides insight into the relationship between folding landscapes and catalysis. The computational approach used here may also provide a powerful strategy for modeling single-molecule experiments and designing enzymes...
  41. pmc Solvation free energies of molecules. The most stable anionic tautomers of uracil
    Maciej Haranczyk
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Phys Chem Chem Phys 10:4442-8. 2008
    ..We found that in water solution three of the recently identified anionic tautomers are 6.5-3.6 kcal mol(-1) more stable than the anion of the canonical tautomer...
  42. pmc Accelerating QM/MM free energy calculations: representing the surroundings by an updated mean charge distribution
    Edina Rosta
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 112:5680-92. 2008
    ..This approach should provide a very powerful tool for QM(ai)/MM evaluation of solvation free energies in aqueous solutions and proteins...
  43. pmc Converting conformational changes to electrostatic energy in molecular motors: The energetics of ATP synthase
    Marek Strajbl
    Department of Chemistry, University of Southern California, Los Angeles, CA 90098 1062, USA
    Proc Natl Acad Sci U S A 100:14834-9. 2003
    ..It is found that the conformational changes are converted to changes in the electrostatic interaction between the protein and its ligands, which drives the ATP synthesis...
  44. ncbi request reprint Simulations of the large kinetic isotope effect and the temperature dependence of the hydrogen atom transfer in lipoxygenase
    Mats H M Olsson
    Chemistry Department, University of Southern California, Los Angeles, California 90089 1062, USA
    J Am Chem Soc 126:2820-8. 2004
    ..We also reached similar conclusions in studies of other enzymes...
  45. ncbi request reprint The low barrier hydrogen bond (LBHB) proposal revisited: the case of the Asp... His pair in serine proteases
    Claudia N Schutz
    Department of Chemistry, University of Southern California, Los Angeles 90089 1062, USA
    Proteins 55:711-23. 2004
    ..The present study provides a support to the idea that enzymes work by creating a preorganized polar environment...
  46. ncbi request reprint Solute solvent dynamics and energetics in enzyme catalysis: the S(N)2 reaction of dehalogenase as a general benchmark
    Mats H M Olsson
    University of Southern California, 3620 McClintock Avenue, Department of Chemistry, SGM418, Los Angeles, California 90089 1062, USA
    J Am Chem Soc 126:15167-79. 2004
    ..It is also shown that the effect of the difference in the relaxation time of the solvent coordinate in the enzyme and solution reaction is rather trivial relative to the effect of the corresponding changes in reorganization free energy...
  47. ncbi request reprint Simulating redox coupled proton transfer in cytochrome c oxidase: looking for the proton bottleneck
    Mats H M Olsson
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    FEBS Lett 579:2026-34. 2005
    ..Although further studies are clearly needed, we believe that our approach offers a general and effective tool for correlating the structure of COX with its function...
  48. ncbi request reprint Computer simulation of the chemical catalysis of DNA polymerases: discriminating between alternative nucleotide insertion mechanisms for T7 DNA polymerase
    Jan Florian
    Department of Chemistry, Loyola University Chicago, Chicago, Illinois 60626, USA
    J Am Chem Soc 125:8163-77. 2003
    ..The relative height of these barriers comparing right and wrong dNTP substrates should therefore be a primary focus of future computational studies of the fidelity of DNA polymerases...
  49. ncbi request reprint Apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization
    Marek Strajbl
    Department of Chemistry, University of Southern California, Los Angeles, California 90098 1062, USA
    J Am Chem Soc 125:10228-37. 2003
    ..However, since the charge distribution of the transition state and the reactant state is similar, the stabilization of the transition state leads to reduction in the distance between the reacting atoms in the reactant state...
  50. ncbi request reprint Computer simulation studies of the fidelity of DNA polymerases
    Jan Florian
    Department of Chemistry, University of Southern California, Los Angeles, CA 90089 1062, USA
    Biopolymers 68:286-99. 2003
    ....
  51. ncbi request reprint Computer simulations of enzyme catalysis: methods, progress, and insights
    Arieh Warshel
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Annu Rev Biophys Biomol Struct 32:425-43. 2003
    ..Finally, it is pointed out that although some of the issues are likely to remain controversial for some time, computer modeling approaches can provide a powerful tool for understanding enzyme catalysis...
  52. ncbi request reprint Dynamical contributions to enzyme catalysis: critical tests of a popular hypothesis
    Mats H M Olsson
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Chem Rev 106:1737-56. 2006
  53. ncbi request reprint Simulating the effect of DNA polymerase mutations on transition-state energetics and fidelity: evaluating amino acid group contribution and allosteric coupling for ionized residues in human pol beta
    Yun Xiang
    Department of Chemistry, University of Southern California, Seeley G Mudd 418, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 45:7036-48. 2006
    ..We discuss the potential of direct calculations of binding energy of the TS in a rational design of TS analogues and in drug design...
  54. ncbi request reprint Realistic simulations of proton transport along the gramicidin channel: demonstrating the importance of solvation effects
    Sonja Braun-Sand
    University of Southern California, Los Angeles, California 90089, USA
    J Phys Chem B 109:583-92. 2005
    ..This finding has clear consequences with regards to PTR processes in biological systems...
  55. ncbi request reprint Simulating large nuclear quantum mechanical corrections in hydrogen atom transfer reactions in metalloenzymes
    Mats H M Olsson
    Chemistry Department, SGM 418, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    J Biol Inorg Chem 9:96-9. 2004
    ..The simulation reproduces quite well the experimental kinetic information and the corresponding difference between the classical and quantum mechanical activation free energies for the H and D transfer reactions...
  56. pmc Monte Carlo simulations of proton pumps: on the working principles of the biological valve that controls proton pumping in cytochrome c oxidase
    Mats H M Olsson
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, SGM418, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 103:6500-5. 2006
    ....
  57. ncbi request reprint Frozen density functional free energy simulations of redox proteins: computational studies of the reduction potential of plastocyanin and rusticyanin
    Mats H M Olsson
    Chemistry Department, University of Southern California, 3620 McClintock Avenue, SGM 418, Los Angeles, California 90089 0047, USA
    J Am Chem Soc 125:5025-39. 2003
    ..This electrostatic environment, which is the major effect determining the reduction potential, is a property of the entire protein and solvent system and cannot be ascribed to any particular single interaction...
  58. ncbi request reprint Simulations of ion current in realistic models of ion channels: the KcsA potassium channel
    A Burykin
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 47:265-80. 2002
    ..The ability to simulate the current in realistic models of ion channels should provide a powerful tool for studies of the biologic function of such systems, including the analysis of the effect of mutations, pH, and electric potentials...
  59. ncbi request reprint Electrostatic effects in macromolecules: fundamental concepts and practical modeling
    A Warshel
    Department of Chemistry, University of Southern California, Los Angeles 90089, USA
    Curr Opin Struct Biol 8:211-7. 1998
    ....
  60. pmc A computational study of the hydrolysis of dGTP analogues with halomethylene-modified leaving groups in solution: implications for the mechanism of DNA polymerases
    Shina C L Kamerlin
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089, USA
    Biochemistry 48:5963-71. 2009
    ..An understanding of the mechanism of this reaction in solution could thereby provide a steppingstone for understanding the factors governing the fidelity of DNA polymerases...
  61. pmc Computer simulations of enzyme catalysis: finding out what has been optimized by evolution
    A Warshel
    Department of Chemistry, University of Southern California, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 95:5950-5. 1998
    ..Apparently, the catalytic power of enzymes is stored in their folding energy in the form of the preorganized polar environment...
  62. pmc Toward accurate screening in computer-aided enzyme design
    Maite Roca
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Biochemistry 48:3046-56. 2009
    ....
  63. pmc On unjustifiably misrepresenting the EVB approach while simultaneously adopting it
    Shina C L Kamerlin
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089, USA
    J Phys Chem B 113:10905-15. 2009
    ..which where presented as verification of the unreliability of the EVB model were in fact obtained by the use of incorrect parameters, without comparing to the correct surface obtained by our program...
  64. pmc Exploring challenges in rational enzyme design by simulating the catalysis in artificial kemp eliminase
    Maria P Frushicheva
    Department of Chemistry, 418 SGM Building, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 107:16869-74. 2010
    ....
  65. ncbi request reprint Why does the Ras switch "break" by oncogenic mutations?
    Avital Shurki
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 55:1-10. 2004
    ..This "allosteric" effect causes a major reduction in the electrostatic stabilization of the TS. Our findings have general relevance to other proteins that control signal transduction processes...
  66. pmc Progress in ab initio QM/MM free-energy simulations of electrostatic energies in proteins: accelerated QM/MM studies of pKa, redox reactions and solvation free energies
    Shina C L Kamerlin
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 113:1253-72. 2009
    ....
  67. pmc A new paradigm for electrostatic catalysis of radical reactions in vitamin B12 enzymes
    Pankaz K Sharma
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Proc Natl Acad Sci U S A 104:9661-6. 2007
    ..The trick used by B(12) enzymes may, in fact, be a very powerful new strategy in enzyme design...
  68. ncbi request reprint On the mechanism of hydrolysis of phosphate monoesters dianions in solutions and proteins
    Marco Klahn
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    J Am Chem Soc 128:15310-23. 2006
    ....
  69. pmc Absolute binding free energy calculations: on the accuracy of computational scoring of protein-ligand interactions
    Nidhi Singh
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 78:1705-23. 2010
    ..Overall, the PDLD/S-LRA/beta appears to offer an appealing option for the final stages of massive screening approaches...
  70. ncbi request reprint Towards accurate ab initio QM/MM calculations of free-energy profiles of enzymatic reactions
    Edina Rosta
    Department of Chemistry, University of Southern California, 3620 South McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 110:2934-41. 2006
    ..Our advance allows one to explore consistently various mechanistic and catalytic proposals while using ab initio (ai) QM/MM approaches...
  71. ncbi request reprint Advances in methods and algorithms in a modern quantum chemistry program package
    Yihan Shao
    Department of Chemistry, University of California, Berkeley, CA 94720, USA
    Phys Chem Chem Phys 8:3172-91. 2006
    ....
  72. ncbi request reprint Calculation of the redox potentials of iron-sulfur proteins: the 2-/3-couple of [Fe4S*4Cys4] clusters in Peptococcus aerogenes ferredoxin, Azotobacter vinelandii ferredoxin I, and Chromatium vinosum high-potential iron protein
    G M Jensen
    Department of Chemistry, University of Southern California, Los Angeles 90089
    Biochemistry 33:10911-24. 1994
    ..In contrast, the results for Cluster II differ substantially; for reasons not yet clear, the recently revised structure leads to results in worse agreement with experiment...
  73. ncbi request reprint Electrostatic basis for bioenergetics
    Avital Shurki
    Department of Chemistry, University of Southern California, Los Angeles 90089, USA
    Methods Enzymol 380:52-84. 2004
  74. ncbi request reprint Molecular dynamics simulations of biological reactions
    Arieh Warshel
    Department of Chemistry, University of Southern California, University Park Campus, Los Angeles, California 90089 1062, USA
    Acc Chem Res 35:385-95. 2002
    ..The resulting insight is crucial in studies of fast photobiological reactions and instructive in cases of slower processes...
  75. ncbi request reprint Exploring the origin of the ion selectivity of the KcsA potassium channel
    Anton Burykin
    Department of Chemistry, University of Southern California, Los Angeles, California 90089 1062, USA
    Proteins 52:412-26. 2003
    ....
  76. ncbi request reprint Using the constrained DFT approach in generating diabatic surfaces and off diagonal empirical valence bond terms for modeling reactions in condensed phases
    Gongyi Hong
    Department of Chemistry, University of Southern California, 3620 S McClintock Ave, Los Angeles, 90089 1062, USA
    J Phys Chem B 110:19570-4. 2006
    ..It is found that, at least for the test case of S(N)()2 reactions, the off diagonal element does not change significantly upon moving from the gas phase to solutions and thus the EVB assumption is valid and extremely useful...
  77. ncbi request reprint What are the roles of substrate-assisted catalysis and proximity effects in peptide bond formation by the ribosome?
    Pankaz K Sharma
    University of Southern California, SGM 418, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 44:11307-14. 2005
    ..The nature of these effects and their relationship to catalytic factors in modern enzymes is analyzed and discussed...
  78. ncbi request reprint Simulation of tunneling in enzyme catalysis by combining a biased propagation approach and the quantum classical path method: application to lipoxygenase
    Janez Mavri
    National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia
    J Phys Chem B 112:5950-4. 2008
    ..In particular, this approach can be used to evaluate the quantum mechanical transmission factor or other dynamical effects, while still obtaining reliable quantized activation free energies due to the QCP correction...
  79. ncbi request reprint Using a charging coordinate in studies of ionization induced partial unfolding
    Mitsunori Kato
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 110:11566-70. 2006
    ....
  80. ncbi request reprint On the generation of catalytic antibodies by transition state analogues
    Montserrat Barbany
    Computational Structural Biology Laboratory, Research Group on Biomedical Informatics GRIB IMIM UPF Passeig Marítim de la Barceloneta 37 49 08003 Barcelona, Spain
    Chembiochem 4:277-85. 2003
    ..The general implications of our findings and the difficulties in designing a perfect TSA are discussed. Finally, the possible use of our approach in screening for an optimal TSA is pointed out...
  81. doi request reprint On the interpretation of the observed linear free energy relationship in phosphate hydrolysis: a thorough computational study of phosphate diester hydrolysis in solution
    Edina Rosta
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    Biochemistry 47:3725-35. 2008
    ..We demonstrate that when this factor is taken into account, it is possible to reproduce the experimental LFER for this system with reasonable accuracy...
  82. pmc The energetics of the primary proton transfer in bacteriorhodopsin revisited: it is a sequential light-induced charge separation after all
    Sonja Braun-Sand
    Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089 1062, USA
    Biochim Biophys Acta 1777:441-52. 2008
    ..This provides the driving force for the subsequent PT steps...
  83. pmc Through the channel and around the channel: Validating and comparing microscopic approaches for the evaluation of free energy profiles for ion penetration through ion channels
    Mitsunori Kato
    Department of Chemistry, University of Southern California, 3620 McClintock Avenue, Los Angeles, California 90089 1062, USA
    J Phys Chem B 109:19516-22. 2005
    ....

Research Grants57

  1. Computer Simulation of Electron and Proton Transfer
    Arieh Warshel; Fiscal Year: 2010
    ..This should assist in the development of effective drugs that will help to fight diseases that are associated with defective charge transport proteins. ..
  2. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2001
    ....
  3. COMPUTER SIMULATION OF ELECTRON TRANSFER REACTIONS
    Arieh Warshel; Fiscal Year: 2000
    ....
  4. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2010
    ..1 ..
  5. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2009
    ..This study will also explore the reason for the difference between the activities of catalytic antibodies and enzymes that catalyze similar reactions. ..
  6. Computer Simulation of Electron and Proton Transfer
    Arieh Warshel; Fiscal Year: 2007
    ..iv) Continuing our studies of the bacterial RCs. (v) Continuing fundamental studies of electrostatic energies in proteins and, (vi) continue our studies of the selectivity of biological ion channels. ..
  7. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2007
    ..This study will also explore the reason for the difference between the activities of catalytic antibodies and enzymes that catalyze similar reactions. ..
  8. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2006
    ..This study will also explore the reason for the difference between the activities of catalytic antibodies and enzymes that catalyze similar reactions. ..
  9. COMPUTER SIMULATION OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 2005
    ..abstract_text> ..
  10. Computer Simulation of Electron and Proton Transfer
    Arieh Warshel; Fiscal Year: 2004
    ....
  11. THEORETICAL STUDIES OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 1980
    ....
  12. COMPUTER SIMULATION OF ELECTRON TRANSFER REACTIONS
    Arieh Warshel; Fiscal Year: 1992
    ..v) The redox potential of electron transfer proteins will be evaluated by free energy perturbation methods. This study will include calculations of the effects of genetic modifications on redox potentials...
  13. COMPUTER SIMULATION OF ELECTRON TRANSFER REACTIONS
    Arieh Warshel; Fiscal Year: 1993
    ..vi) Simulation of ET in solution, using an explicit representation of donor and acceptor, trying to reproduce experimental results of well defined test cases...
  14. THEORETICAL STUDIES OF ENZYMATIC REACTIONS
    Arieh Warshel; Fiscal Year: 1993
    ..In parallel to our fundamental studies we will start to explore the predictive power of our models by simulating the effect of site-directed mutagenesis on rate enhancement of enzymatic reactions...