Table of Contents

Acknowledgment. Congratulations to Professor Ada Yonath for Winning the 2009 Nobel Prize in Chemistry. Introductory Reflections on Quantum Biochemistry: From Context to Contents (Cherif F. Matta). List of Contributors. Vol I. Part One. Novel Theoretical, Computational, and Experimental Methods and Techniques. 1. Quantum Kernels and Quantum Crystallography: Applications in Biochemistry (Lulu Huang, Lou Massa, and Jerome Karle). 1.1 Introduction. 1.2 Origins of Quantum Crystallography (QCr). 1.3 Beginnings of Quantum Kernels. 1.4 Kernel Density Matrices Led to Kernel Energies. 1.5 Summary and Conclusions. References. 2. Getting the Most out of ONIOM: Guidelines and Pitfalls (Fernando R. Clemete, Thom Vreven, and Michael J. Frisch). 2.1 Introduction. 2.2 QM/MM. 2.3 ONIOM. 2.4 Guidelines for the Application of ONIOM. 2.5 The Cancellation Problem. 2.6 Use of Point Charges. 2.7 Conclusions. References. 3. Modeling Enzymatic: Reactions in Metalloenzymes and Photobiology by Quantum Mechanics (QM) and Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations (Lung Wa Chung, Xin Li, and Keiji Morokuma). 3.1 Introduction. 3.2 Computational Strategies (Methods and Models). 3.3 Metalloenzymes. 3.4 Photobiology. 3.5 Conclusion. References. 4. From Molecular Electrostatic Potentials to Solvation Models and Ending with Biomolecular with Biomolecular Photophysical Processes (Jacopo Tomasi, Chiara Cappelli, Benedetta Mennucci, and Roberto Cammi). 4.1 Introduction. 4.2 The Molecular Electrostatic Potential and Noncovalent Interactions among Molecules. 4.3 Solvation: the "Continuum Model." 4.4 Applications of the PCM Method. References. 5. The Fast Marching Method for Determining Chemical Reaction Mechanisms in Complex Systems (Yuli Liu, Steven K. Burger, Bijoy K. Dey, Utpal Sarkar, Marek R. Janicki, and Paul W. Ayers). 5.1 Motivation. 5.2 Background. 5.3 Fast Marching Method. 5.4 Quantum Mechanics/Molecular Mechanics (QM/MM) Methods Applied to Enzyme-Catalyzed Reactions. 5.5 Summary. References. Part Two. Nucleic Acids, Amino Acids, Peptides and Their Interactions. 6. Chemical Origin of Life: How do Five HCN Molecules Combine to form Adenine under Prebiotic and Interstellar Conditions (Debjani Roy and Paul von Rague Schleyer). 6.1 Introduction. 6.2 Computational Investigation. 6.3 Conclusion. References. 7. Hydrogen Bonding and Proton Transfer in ionized DNA Base Pairs, Amino Acids and Peptides (Luis Rodriguez-Santiago, Marc Noguera, Joan Bertran, and Mariona Sodupe). 7.1 Introduction. 7.2 Methodological Aspects. 7.3 Ionization of DNA Base Pairs. 7.4 Ionization of Amino Acids. 7.5 Ionization of Peptides. 7.6 Conclusions. References. 8. To Nano-Biochemistry: Picture of the Interactions of DNA with Gold (Eugene S. Kryachko). 8.1 Introductory Nanoscience Background. 8.2 DNA-Gold Bonding Patterns: Some Experimental Facts. 8.3 Adenine-Gold Interaction. 8.4 GuanineGold Interaction. 8.5 Thymine-Gold Interactions. 8.6 Cytosine-Gold Interactions. 8.7 Basic Trends of DNA Base-Gold Interaction. 8.8 Interaction of Watson-Crick DNA Base Pairs with Gold Clusters. 8.9 Summary. References. 9. Quantum Mechanical Studies of Noncovalent DNA-Protein Intereactions (Lesley R. Rutledge and Stacey D. Wetmore). 9.1 Introduction. 9.2 Computational Approaches for Studying Noncovalent Interactions. 9.3 Hydrogen-Bonding Interactions. 9.4 Interactions between Aromatic DNA-Protein Components. 9.5 Cation-pi Interactions between DNA-Protein Components. 9.6 Conclusions. References. 10. The Virial Field and Transferability in DNA Base-Pairing (Richard F. W. Bader and Fernando Cortes-Guzman). 10.1 A New Theorem Relating the Density of an Atom in a Molecule to the Energy. 10.2 Computations. 10.3 Chemical Transferability and the One-Electron Density Matrix. 10.4 Changes in Atomic Energies Encountered in DNA Base Pairing. 10.5 Energy Changes in the WC Pairs GC and AT. 10.6 Discussion. References. 11. An Electron Density-Based Approach to the Origin of Stacking Interactions (Ricardo A. Mosquera, Maria J. Gonzalez Moa, Laura Estevez, Marcos Mandado, and Ana M. Grana). 11.1 Inroduction. 11.2 Computational Method. 11.3 Charge-Transfer Complexes: Quinhydrone. 11.4 pi-pi Interactions in Hetero-Molecular Complexes: Methyl Gallate-Caffeine Adduct. 11. 5 pi-pi Interactions between SNA Base Pair Steps. 11.6 pi-pi Interactions in Homo-Molecular Complexes: Catechol. 11.7 C-H/pi Complexes. 11.8 Provisional Conclusions and Future Research. References. 12. Polarizabilities of Amino Acids: Additive Models and Ab Initio Calculations (Noureddin El-Bakali Kassimi and Ajit J. Thakkar). 12.1 Introduction. 12.2 Models of Polarizability. 12.3 Polarizabilities of the Amino Acids. 12. 4 Concluding Remarks. References. 13. Methods in Biocomputational Chemistry: A Lesson from the Amino Acids (Hugo J. Boho rquez, Constanza Ca rdenas, Cherif F. Matta, Russel J. Boyd, and Manuel E. Patarroyo). 13.1 Introduction. 13.2 Conformers, Rotamers and Physiochemical Variables. 13.3 QTAIM Side Chain Polarizations and the Theoretical Classification of Amino Acids. 13.4 Quantum Mechanical Studies of Peptide-Host Interactions. 13.5 Conclusions. References. 14. From Atoms in Amino Acids to the Genetic Code and Protein Stability, and Backwards (Cherif F. Matta). 14.1 Context of the Work. 14.2 The Electron Density Q(r) as an Indirectly Measureable Dirac Observable. 14.3 Brief Review of Some Basic Concepts of the Quantum Theory of Atoms in Molecules. 14.4 Computational Approach and Level of Theory. 14.5 Empirical Correlations of QTAIM Atomic Properties of Amino Acid Side Chains with Experiment. 14.6 Molecular Complementarity. 14.7 Closing Remarks. 14.8 Appendix A X-Ray and Neutron Diffraction Geometries of the Amino Acids in the Luterature. References. 15. Energy Richness of ATP in Terms of Atomic Energies: A First Step (Cherif F. Matta and Alya A. Arabi). 15.1 Introduction. 15.2 How "(De)Localized" is the Enthalpy of Bond Dissociation? 15.3 The Choice of a Theoretical Level. 15.4 Computational Details. 15.5 (Global) Energies of the Energy of Hydrolysis of ATP in the Absence and Presence of Mg2+. 15.6 How "(De)Localized" is the Energy of Hydrolysis of ATP? 15.7 Other Changes upon Hydrolysis of ATP in the Presence and Absence of Mg2+. 15.8 Conclusions. References. Vol II Part Three. Reactivity, Enzyme, Biochemical Reaction Paths and Mechanisms. 16. Quantum Transition State for Peptide Bon Formation in the Ribosome (Lou Massa, Cherif F. Matta, Ada Yonath, and Jerome Karle). 16.1 Introduction. 16.2 Methodology: Searching for the Transition State and Calculating its Properties. 16.3 Results: The Quantum Mechanical Transition State. 16.4 Discussion. 16.5 Summary and Conclusions. References. 17. Hydrid QM-MM Simulations of Enzyme-Catalyzed DNA Repair Reactions (Denis Bucher, Fanny Masson, J. Samuel Arey, and Ursula Rothlisberger). 17.1 Introduction. 17.2 Theoretical Background. 17.3 Applications. 17.4 Conclusions. References. 18. Computational Electronic Structure of Spin-Coupled Diiron-Oxo Protein (Jorge H. Rodqiguez). 18.1 Introduction. 18.2 (Anti)ferromagnetic Spin Coupling. 18.3 Spin Density Functional Theory of Antiferromagnetic Diiron Complexes. 18.4 Phenomenological Simulation of Mossbauer Spectra of Diiron-oxo Proteins. 18.5 Conclusion. References. 19. Accurate Description of Spin States and its Implications for Catalysis (Marcel Swart, Mireia Guell, and Miquel Sola ). 19.1 Introduction. 19.2 Influence of the Basis Set. 19.3 Spin-Contamination Corrections. 19.4 Influence of Self-Consistency. 19.5 Spin-States of Model Complexes. 19.6 Spin-States Involved in Catalytic Cycles. 19.7 Concluding Remarks. 19.8 Computational Details. References. 20. Quantum Mechanical Approaches to Selenium Biochemistry (Jason K. Pearson and Russell J. Boyd). 20.1 Introduction. 20.2 Quantum Mechanical Methods for the Treatment of Selenium. 20.3 Applications to Selenium Biochemistry. 20.4 Summary. References. 21. Catalytic Mechanism of Metallo beta-Lactamases: Insights from Calculations and Experiments (Matteo Dal Peraro, Alejandro J. Vila, and Paolo Carloni). 21.1 Introduction. 21.2 Structural Information. 21.3 Computational Details. 21.4 Preliminary Comment on the Comparison between Theory and Experiment. 21.5 Michaelis Complex in B1 MbetaLs. 21.6 Catalytic Mechanism of B1 MbetaLs. 21.7 Michaelis Complexes of other MbetaLs. 21.8 Concluding Remarks. References. 22. Computational Simulation of the Terminal Biogenesis of Sesquiterpenes: The Case of 8-Epiconfertin (Jose Enrique Barquera-Lozada and Gabriel Cuevas). 22.1 Introduction. 22.2 Reaction Mechanism. 22.3 Conclusions. References. 23. Mechanistics of Enzyme Catalysis: From Small to Large Active-Site Models (Jorge Llano and James W. Gauld). 23.1 Introduction. 23.2 Active-Site Models of Enzymatic Catalysis: Methods and Accuracy. 23.3 Redox Catalytic Mechanisms. 23.4 General Acid-Base Catalytic Mechanism of Deacetylation in LpxC. 23.5 Summary. References. Part Four. From Quantum Biochemistry to Quantum Pharmacology, Therapeutics, and Drug Design. 24. Developing Quantum Topological Molecular Similarity (QTMS) (Paul L. A. Popelier). 24.1 Introduction. 24.2 Anchoring in Physical Organic Chemistry. 24.3 Equilibrium Bond Lengths:"Threat" or "Opportunity"? 24.4 Introducing Chemometrics: Going Beyond r2. 24.5 A Hopping Center of Action. 24.6 A Leap. 24.7 A Couple of General Reflections. 24.8 Conclusions. References. 25. Quantum-Chemical Descriptors in QSAr/QSPR Modeling: Achievements, Perspectives and Trends (Anna V. Gubskaya). 25.1 Introduction. 25.2 Quantum-Chemical Methods and Descriptors. 25.3 Computational Approaches for Establishing Quantitative Structure-Activity Relationships. 25.4 Quantum-Chemical Descriptors in QSAR/QSPR Models. 25.5 Summary and Conclusions. References. 26. Platinum Complexes as Anti-Cancer Drugs: Modeling of Structure, Activation and Function (Kanstantinos Gkionis, Mark Hicks, Arturo Robertazzi, J. Grant Hill, and James A. Platts). 26.1 Introduction to Cisplatin Chemistry and Biochemistry. 26.2 Calculation of Cisplatin Structure, Activation and DNA Interactions. 26.3 Platinum-Based Alternatives. 26.4 Non-platinum Alternatives. 26.5 Absorption, Distribution, Metabolism, Excretion (ADME) Aspects. References. 27. Protein Misfolding: The Quantum Biochemical Search for a Solution to Alzheimer's Disease (Donald F. Weaver). 27.1 Introduction. 27.2 Protein Folding and Misfolding. 27.3 Quantum Biochemistry in the Study of Protein Misfolding. 27.4 Alzheimer's Disease: A Disorder of Protein Misfolding. 27.5 Quantum Biochemistry and Designing Drugs for Alzheimer's Disease. 27.6 Conclusions. References. 28. Targeting Butyrylcholinesterase for Alzheimer's Disease Therapy (Katherine V. Darvesh, Ian R. Pottie, Robert S. McDonald, Earl Martin, and Sultan Darvesh). 28.1 Butyrylcholinesterase and the Regulation of Cholinergic Neurotransmission. 28.2 Butyrylcholinesterase: The Significant other Cholinesterase, in Sickness and in Health. 28.3 Optimizing Specific Inhabitors of Butyrylcholinesterase Based on the Phenothiazine Scaffold. 28.4 Biological Evaluation of Phenothiazine Derivative as Cholinesterase Inhibitors. 28.5 Computation of Physical Parameters to Interpret Structure-Activity Relationships. 28.6 Enzyme-Inhabitor Structure-Activity Relationships. 28.7 Conclusions. References. 29. Reduction Potentials of Peptide-Bound Copper (II) - Relevance for Alzheimer's Disease and Prion Diseases (Arvi Rauk). 29.1 Introduction. 29.2 Copper Binding 1n Albumin - Type 2. 29.3 Cooper Binding to Cerulopjasmin - Type 1. 29.4 The Prion Protein Octarepeat Region. 29.5 Copper and the Amyloid Beta Peptide (Abeta) of Alzheimer's Disease. 29.6 Cu(II)/Cu(I) Reduction Potentials in Cu/Abeta. 29.7 Concluding Remarks. References. 30. Theoretical Investigation of NSAID Photodegradation Mechanisms (Klefah A. K. Musa and Leif A. Eriksson). 30.1 Drug Safety. 30.2 Drug Photosensitivity. 30.3 Non-Steroid Anti-Inflammatory Drugs (NSAIDs). 30.4 NSAID Phototoxicity. 30.5 Theoretical Studies. 30.6 Redox Chemistry. 30.7 NSAID Orbital Structures. 30.8 NSAID Absorption Spectra. 30.9 Excited State Reactions. 30.10 Reactive Oxygen Species (ROS) and Radical Formation. 30.11 Effects of the Formed ROS and Radicals during the Photodegradation Mechanisms. 30.12 Conclusions. References. Part Five. Biochemical Signature of Quantum Indeterminism. 31. Quantum Indeterminism, Mutation, Natural Selection, and the Meaning of Life (David N. Stamos). 31.1 Introduction. 31.2 A Short History of the Debate in Philosophy of Biology. 31.3 Replies to My Paper. 31.4 The Quantum Indeterministic Basis of Mutations. 31.5 Mutation and the Direction of Evolution. 31.6 Mutational Order. 31.7 The Nature of Natural Selection. 31.8 The Meaning of Life. References. 32. Molecular Orbitals: Dispositions or Predictive Structures? (Jean-Pierre Llored and Michel Bitbol). 32.1 Origins of Quantum Models in Chemistry: The Composite and the Aggregate. 32.2 Evolution of the Quantum Approaches and Biology. 32.3 Philosophical Implications of Molecular Quantum Holism: Dispositions and Predictive Structures. 32.4 Closing Remarks. References. Index.

About the Author

Cherif F. Matta is Associate Professor at the Department of Chemistry and Physics, Mount Saint Vincent University and an Honorary Adjunct Professor at the Department of Chemistry, Dalhousie University, both in Halifax, Canada. He obtained his BSc from Alexandria University, Egypt, in 1987 and gained his PhD in theoretical chemistry from McMaster University, Canada, in 2002. He was then a postdoctoral fellow at the University of Toronto, Canada, before being awarded an I. W. Killam Fellowship at Dalhousie University. In addition to his current academic appointments, which started in 2006, he has held adjunct/visiting Professorships at McMaster University and at the Universite Henri Poincare (UHP), Nancy Universite ? 1. In 2009, he received the HDR (Habilitation) degree from the UHP. Professor Matta has published more than 50 research papers and book chapters, and edited the Quantum Theory of Atoms in Molecules: From Solid State to DNA and Drug Design (Wiley-VCH, 2007) with Russell J. Boyd. He is the recipient of the Molecular Graphics and Molecular Simulation Society Silver Jubilee Prize for 2009 and won the John C. Polanyi Prize in Chemistry in 2004. His research is in theoretical and computational chemistry with a focus on the analysis of molecular electron densities and its applications.