Theoretical chemistry has been an area of tremendous expansion and development over the past decade; from an approach where we were able to treat only a few atoms quantum mechanically or make fairly crude molecular dynamics simulations, into a discipline with an accuracy and predictive power that has rendered it an essential complementary tool to experiment in basically all areas of science.
This volume gives a flavour of the types of problems in biochemistry that theoretical calculations can solve at present, and illustrates the tremendous predictive power these approaches possess.
A wide range of computational approaches, from classical MD and Monte Carlo methods, via semi-empirical and DFT approaches on isolated model systems, to Car-Parinello QM-MD and novel hybrid QM/MM studies are covered. The systems investigated also cover a broad range; from membrane-bound proteins to various types of enzymatic reactions as well as inhibitor studies, cofactor properties, solvent effects, transcription and radiation damage to DNA.
For experimental and research chemists and biochemists who use theoretical and computational techniques in their work.
Theoretical Biochemistry, 1st Edition
The Structure and Function of Blue Copper Proteins
M.H.M. Olsson and K. Pierloot). Introduction. Methods. Geometry. Electronic spectra. Reorganisation energies. Reduction potentials. Related proteins. Protein strain. Concluding remarks. Myoglobin
(D. Karancsi-Menyhárd, G. Keserü and G. Náray-Szabó). Introduction. Conformation and structural dynamics. Complexes with various ligands. Photodissociation. Recombination. Ligand migration. Mechanisms for Enzymatic Reactions Involving Formation or
Cleavage of O-O Bonds
(P.E.M. Siegbahn and M.R.A. Blomberg). Introduction. Methods and models. Formation of O2
. O-O bond cleavage. Conclusions. Catalytic Reactions of Radical Enzymes
(F. Himo and L.A.
Eriksson). Introduction. Methodology. Galactose oxidase. Pyruvate formate-lyase. Ribonucleotide reductase. Concluding remarks. Theoretical Studies of Coenzyme B12-Dependent Carbon-Skeleton Rearrangements
(D.M. Smith, S.D. Wetmore and L. Radom). Introduction. Background. Evaluation of theoretical techniques. 2-Methyleneglutarate mutase. Methylmalonyl-CoA mutase. Glutamate mutase. Comparison of the models for B12
-dependent carbon-skeleton mutases. The partial-proton-transfer concept. Conclusions. Simulations of Enzymatic Systems: Perspectives from Car-Parinello Molecular Dynamics Simulations
(P. Carloni and U. Rothlisberger). Introduction. Principles of the Car-Parinello method. Car-Parinello modelling of biological systems. Applications to non-enzymatic systems. Applications to enzymes. Outlook. Computational Enzymology: Protein Tyrosine Phosphatase Reactions
(K. Kolmodin, V. Luzhkov and J. Åqvist). Introduction. Protein tyrosine phosphatase reactions. The empirical valence bond method. Reaction free energy profile of the LMPTP. Substrate trapping in cysteine to serine mutated PTPases. Prediction of a ligand induced conformational change in the active site of CDC25A. Kinetic isotope effects in phosphoryl transfer reactions. Monte Carlo Simulations of HIV-1 Protease Binding Dynamics and Thermodynamics with Ensembles of Protein Conformations: Incorporating Protein Flexibility in Deciphering Mechanisms of Molecular Recognition
(G.M. Verkhivker, D. Bouzida, D.K. Gehlhaar, P.A. Rejto, L. Schaffer, S. Arthurs, A.B. Colson, S.T. Freer, V. Larson, B.A: Luty, T. Marrone and P.W. Rose). Structural models for molecular recognition. Structure-based analysis of HIV-1 protease-inhibitor binding. Structure-based computational models of ligand-protein binding dynamics and molecular docking. Computer simulations of ligand-protein binding. Computer simulations of HIV-1 protease-inhibitor binding dynamics and thermodynamics. Conclusions. Modelling G-Protein Coupled Receptors
(C. Higgs and C.A. Reynolds). Introduction. Receptor structure and modelling. Ligand binding. Structural changes. Receptor-G-protein interactions. GPCR dimerisation. Conclusions. Protein-DNA Interactions in the Initiation of Transcription: The Role of Flexibility and Dynamics of the TATA Recognition Sequence and the TATA Box Binding Protein
(N. Pastor and H. Weinstein). TBP and transcription. TATA box sequence specific recognition. Dynamics effects in complex stabilization. Towards the preinitiation complex assembly. Concluding remarks. A Multi-Component Model for Radiation Damage to DNA
from its Components
(S.D. Wetmore, L.A. Eriksson and R.J.
Boyd). Introduction. Characterization of DNA radiation products. Full DNA studies. Multi-component model for DNA radiation damage. Concluding remarks. New Computational Strategies for the Quantum Mechanical Study of Biological Systems in Condensed Phases
M. Cossi, N. Rega and V. Barone). Introduction. The density functional model. Vibrational averaging. Solvent effects. Applications. Concluding remarks. Modelling Enzyme-Ligand Interactions
(M.J. Ramos, A. Melo
and E.S. Henriques). Introduction. Strategies in enzyme-ligand design. The enzyme-ligand complex in motion. A quantum insight into the study of enzyme-ligand interactions. Conclusions. The QM/MM Approach to Enzymatic Reactions
Mulholland). Introduction. Theory. QM/MM methods. Techniques for reaction modelling. Practical aspects of modelling enzyme reactions. Some recent applications. Conclusions. Quinones and Quinoidal Radicals in Photosynthesis
(R.A. Wheeler). Introduction. Tests of computational methods for calculating properties of quinoidal radicals. Calculated properties of quinoidal radicals important in photosynthesis. Semiquinone radical anions in plant photosystem II. Conclusion and future directions. Author Index. Subject Index.
Quotes and reviews
@from:A.S. Edison, University of Florida
@qu:"Researchers working on any of the applications covered in the book will find very stimulating chapters that do a fine job of demonstrating the power of combining theory with experiment."
@source:Journal of the American Chemical Society, 2002