Электронная книга: Arieh Warshel «Theory and Applications of the Empirical Valence Bond Approach. From Physical Chemistry to Chemical Biology»

Arieh Warshel

Arieh Warshel is a professor of Chemistry and Biochemistry at the University of Southern California.

Known for his work on Computational biochemistry and biophysics, he is the originator of modern force field approaches where the use of Cartesian coordinates allowed the treatment of energy structure an vibrations of any molecule or molecular crystal as well as the refinement of force field by the so-called consistent force field (CFF) [cite journal |author=Lifson S, Warshel A.|year= 1968| title=A Consistent Force Field for Calculation on Conformations, Vibrational Spectra and Enthalpies of Cycloalkanes and n-Alkane Molecules| journal = J. Phys. Chem.| volume=49| pages=5116| doi=10.1063/1.1670007] [ cite journal |author=Warshel A, Lifson S.|year=1970| title=Consistent Force Field Calculations. II. Crystal Structure, Sublimation Energies, Molecular and Lattice Vibrations, Molecular Conformations and Enthalpies of Alkanes| journal= J. Chem. Phys.| volume=53| pages=582| doi=10.1063/1.1674031] . The CFF code written with Michael Levitt has been the basis for basically all current biological molecular modeling programs (e.g., CHARMM, AMBER, GROMOS, DISCOVERY etc.).

Warshel and his coworkers have introduced the key approaches and concepts in modeling biological functions. These include the development of the simplified folding model [cite journal |author=Levitt M, Warshel A.| year=1975| title=Computer Simulations of Protein Folding| journal=Nature| volume=253|pages=694| doi=10.1038/253694a0] , the introduction of MD simulations of Biological processes [cite journal |author=Warshel A.| year=1976| title=Bicycle-pedal Model for the First Step in the Vision Process| journal=Nature| volume=260|pages=679| doi=10.1038/260679a0] [cite journal |author=Warshel A.| year=2002|title=Molecular Dynamics Simulations of Biological Reactions| journal=Acc. Chem. Res.| volume=35|pages=385–395|doi=10.1021/ar010033z] , and the introduction of the first description of the catalytic effect in an entire enzyme-substrate complex solvated by Langevin dipoles cite journal| author=Warshel A, Levitt M| year=1976| title=Theoretical Studies of Enzymatic Reactions: Dielectric Electrostatic and Steric Stabilization of the Carbonium Ion in the Reaction of Lysozyme| journal=J. Mol. Biol.| volume=103| pages=227| doi=10.1016/0022-2836(76)90311-9] . This constituted the foundation of the combined quantum mechanical/molecular mechanics (QM/MM) method and of consistent modeling of enzymatic reactions cite journal| author=Warshel A, Levitt M| year=1976| title=Theoretical Studies of Enzymatic Reactions: Dielectric Electrostatic and Steric Stabilization of the Carbonium Ion in the Reaction of Lysozyme| journal=J. Mol. Biol.| volume=103|pages=227| doi=10.1016/0022-2836(76)90311-9] . He clarified the relationship between reactions in solution and enzymes and established the catalytic role of preorganized active sites [ cite journal| author=Warshel A| year=1978| title=Energetics of Enzyme Catalysis| journal=Proc. Natl. Acad. Sci. USA| volume=75| pages=5250| doi=10.1073/pnas.75.11.5250] and introduced the empirical valence bond (EVB) for simulation dynamics and free energies of enzymatic reactions [ cite journal| author=Warshel A, Weiss R M.| year=1980| title=An Empirical Valence Bond Approach for Comparing Reactions in Solutions and in Enzymes|journal=J. Am. Chem. Soc.| volume=102|pages=6218| doi=10.1021/ja00540a008] [cite journal| author=Warshel A| year=1984| title=Dynamics of Enzymatic Reactions| journal=Proc. Natl. Acad. Sci.USA| volume=81| pages=444| doi=10.1073/pnas.81.2.444] .

Warshel introduced microscopically based thermodynamic cycles to studies of biological processes [ cite journal| author=Warshel A| title=Calculations of Enzymic Reactions: Calculations of pKa, Proton Transfer Reactions, and General Acid Catalysis Reactions in Enzymes| journal=Biochemistry| volume=20|pages=3167| doi=10.1021/bi00514a028| year=1981] and was the first to introduce free energy perturbations (FEP) in studies of proteins [cite journal|author=Warshel A|year=1984|title=Simulating the Energetics and Dynamics of Enzymatic Reactions|journal=Pontificiae Academiae Scientiarum Scripta Varia| volume=55|pages=60] [cite journal|author=Warshel A, Sussman F, King G.| year=1986|title=Free Energy of Charges in Solvated Proteins: Microscopic Calculations Using a Reversible Charging Process| journal=Biochemistry| volume=25|pages=8368|doi=10.1021/bi00374a006] , and thus, opened the way for microscopic free energy studies of protein functions.

Warshel introduced microscopic calculations of electrostatic energies in proteins cite journal| author=Warshel A, Levitt M| year=1976| title=Theoretical Studies of Enzymatic Reactions: Dielectric Electrostatic and Steric Stabilization of the Carbonium Ion in the Reaction of Lysozyme| journal=J. Mol. Biol.| volume=103|pages=227| doi=10.1016/0022-2836(76)90311-9] [cite journal| author=Warshel A, Russell S T.| year=1984|title=Calculations of Electrostatic Interactions in Biological Systems and in Solutions| journal=Quart. Rev. Biophys.| volume=17|pages=283] and demonstrated the overriding importance of electrostatic interactions in protein functions and paved the way for quantitative studies of electrostatic energies in macromolecules [cite journal|author=Warshel A, Sharma P K, Kato M, Parson W W.| year=2006| title=Modeling Electrostatic Effects in Proteins| journal=Biochim. Biophys. Acta| volume=1764| pages=1647–1676] .

References

External links

* [http://laetro.usc.edu/ Warshel research group at the University of Southern California]
* [http://chem.usc.edu/faculty/Warshel.html Warshel's faculty website at USC]

Источник: Arieh Warshel