Quantum Biochemistry

VOLUME ONE

PART I: Novel Theoretical , Computational, and Experimental Methods and Techniques

QUANTUM KERNELS AND QUANTUM CRYSTALLOGRAPHY: APPLICATIONS IN BIOCHEMISTRY
Introduction
Origins of Quantum Crystallography (QCr)
Beginnings of Quantum Kernels
Kernel Density Matrices Led to Kernel Energies
Summary and Conclusions
GETTING THE MOST OUT OF ONIOM: GUIDELINES AND PITFALLS
Introduction
QM/MM
ONIOM
Guidelines for the Application of ONIOM
Use of Point charges
Conclusions
MODELING ENZYMATIC REACTIONS IN METALLOENZYMES AND PHOTOBIOLOGY BY QUANTUM MECHANICS (QM) AND QUANTUM MECHANICS/MOLECULAR MECHANICS (QM/MM) CALCULATIONS
Introduction
Computational Strategies (Methods and Models)
Metalloenzymes
Photobiology
Conclusion
FROM MOLECULAR ELECTROSTATIC POTENTIALS TO SOLVATION MODELS AND ENDING WITH BIOMOLECULAR PHOTOPHYSICAL PROCESSES
Introduction
The Molecular Electrostatic Potential and Noncovalent Interactions among Molecules
Solvation: The "Continuum Model"
Applications of the PCM Method
THE FAST MARCHING METHOD FOR DETERMINING CHEMICAL REACTION MECHANISMS IN COMPLEX SYSTEMS
Motivation
Background
Fast Marching Method
Quantum Mechanics/Molecular Mechanics (QM/MM) Methods Applied to Enzyme-Catalyzed Reactions
Summary

PART II: Nucleic Acids, Amino Acids, Peptides and Their Interactions

CHEMICAL ORIGIN OF LIFE: HOW DO FIVE HCN MOLECULES COMBINE TO FORM ADENINE UNDER PREBIOTIC AND INTERSTALLAR CONDITIONS
Introduction
Prebiotic Chemistry: Experimental Endeavor to Synthesize the Building Blocks of Biopolymers
Computational Investigation
Conclusion
HYDROGEN BONDING AND PROTON TRANSFER IN IONIZED DNA BASE PAIRS, AMINO ACIDS AND PEPTIDES
Introduction
Methodological Aspects
Ionization of DNA Base Pairs
Ionization of Amino Acids
Ionization of Peptides
Conclusions
TO NANO-BIOCHEMISTRY: PICTURE OF THE INTERACTIONS OF DNA WITH GOLD
Introductory Nanoscience Background
DNA-Gold Bonding Patterns: Some Experimental Facts
Adenine-Gold Interaction
Guanine-Gold Interaction
Thymine-Gold Interactions
Cytosine-Gold Interactions
Basic Trends of DNA Base-Gold Interaction
Interaction of Watson-Crick DNA Base Pairs with Gold Clusters
Summary and Perspectives
QUANTUM MECHANICAL STUDIES OF NONCOVALENT DNA-PROTEIN INTERACTIONS
Introduction
Computational Approaches for Studying Noncovalent Interactions
Hydrogen-Bonding Interactions
Interactions between Aromatic DNA-Protein Components
Cation-pi Interactions between DNA-Protein Components
Conclusions
THE VIRIAL FIELD AND TRANSFERABILITY IN DNA BASE-PAIRING
A New Theorem Relating the Density of an Atom in a Molecule to the Energy
Computations
Chemical Transferability and the One-Electron Density Matrix
Changes in Atomic Energies Encountered in DNA Base Pairing
Energy Changes in the WC Pairs GC and AT
Discussion
AN ELECTRON DENSITY-BASED APPROACH TO THE ORIGIN OF STACKING INTERACTIONS
Introduction
Computational Method
Charge-Transfer Complexes: Quinhydrone
pi-pi Interactions in Hetero-Molecular Complexes: Methyl Gallate-Caffeine Adduct
pi-pi Interactions between DNA Base Pair Steps
pi-pi Interactions in Homo-Molecular Complexes: Catechol
C-H/pi Complexes
Provisional Conclusions and Future Research
POLARIZABILITIES OF AMINO ACIDS: ADDITIVE MODELS AND AB INITIO CALCULATIONS
Introduction
Models of Polarizability
Polarizabilities of the Amino Acids
Concluding Remarks
METHODS IN BIOCOMPUTATIONAL CHEMISTRY: A LESSON FROM THE AMINO ACIDS
Introduction
Conformers, Rotamers and Physicochemical Variables
QTAIM Side Chain Polarizations and the Theoretical Classification of Amino Acids
Quantum Mechanical Studies of Peptide-Host Interactions
Conclusions
FROM ATOMS IN AMINO ACIDS TO THE GENETIC CODE AND PROTEIN STABILITY, AND BACKWARDS
Context of the Work
The Electron Density rho(r) as an Indirectly Measurable Dirac Observable
Brief Review of Some Basic Concepts of the Quantum Theory of Atoms in Molecules
Computational Approach and Level of Theory
Empirical Correlations of QTAIM Atomic Properties of Amino Acid Side Chains with Experiment
Molecular Complementarity
Closing Remarks
Appendix A: X-Ray and Neutron Diffraction Geometries of the Amino Acids in the Literature
ENERGY RICHNESS OF ATP IN TERMS OF ATOMIC ENERGIES: A FIRST STEP
Introduction
How "(De)Localized" is the Enthalpy of Bond Dissociation?
The Choice of a Theoretical Level
Computational Details
(Global) Energies of the Hydrolysis of ATP in the Absence and Presence of Mg2+
How "(De)Localized" is the Energy of Hydrolysis of ATP?
Other Changes upon Hydrolysis of ATP in the Presence and Absence of Mg2+
Conclusions

VOLUME TWO

PART III: Reactivity, Enzyme Catalysis, Biochemical Reaction Paths and Mechanisms

QUANTUM TRANSITION STATE FOR PEPTIDE BOND FORMATION IN THE RIBOSOME
Introduction
Methodology: Searching for the Transition State and Calculating its Properties
Results: The Quantum Mechanical Transition State
Discussion
Summary and Conclusions
HYBRID QM/MM SIMULATIONS OF ENZYME-CATALYZED DNA REPAIR REACTIONS
Introduction
Theoretical Background
Applications
Conclusions
COMPUTATIONAL ELECTRONIC STRUCTURE OF SPIN-COUPLED DIIRON-OXO PROTEINS
Introduction
(Anti)ferromagnetic Spin Coupling
Spin Density Functional Theory of Antiferromagnetic Diiron Complexes
Phenomenological Simulation of Mössbauer Spectra of Diiron-Oxo Proteins
Conclusion
ACCURATE DESCRIPTION OF SPIN STATES AND ITS IMPLICATIONS FOR CATALYSIS
Introduction
Influence of the Basis Set
Spin-Contamination Corrections
Influence of Self-Consistency
Spin-States of Model Complexes
Spin-States Involved in Catalytic Cycles
Concluding Remarks
Computational Details
QUANTUM MECHANICAL APPROACHES TO SELENIUM BIOCHEMISTRY
Introduction
Quantum Mechanical Methods for the Treatment of Selenium
Applications to Selenium Biochemistry
Summary
CATALYTIC MECHANISM OF METALLO BETA-LACTAMASES: INSIGHTS FROM CALCULATIONS AND EXPERIMENTS
Introduction
Structural Information
Computational Details
Preliminary Comment on the Comparison between Theory and Experiment
Michaelis Complex in B1 MBetaLs
Catalytic Mechanism of B1 MBetaLs
Michaelis Complexes of other MBetaLs
Concluding Remarks
COMPUTATIONAL SIMULATION OF THE TERMINAL BIOGENESIS OF SESQUITERPENES: THE CASE OF 8-EPICONFERTIN
Introduction
Reaction Mechanism
Conclusions
MECHANISTICS OF ENZYME CATALYSIS: FROM SMALL TO LARGE ACTIVE-STIE MODELS
Introduction
Active-Site Models of Enzymatic Catalysis: Methods and Accuracy
Redox Catalytic Mechanisms
General Acid-Base Catalytic Mechanism of Deacetylation in LpxC
Summary

PART IV: From Quantum Biochemistry to Quantum Pharmacology, Therapeutics, and Drug Design

DEVELOPING QUANTUM TOPOLOGICAL MOLECULAR SIMILARITY (QTMS)
Introduction
Anchoring in Physical Organic Chemistry
Equilibrium Bond Lengths: "Threat" or "Opportunity"?
Introducing Chemometrics: Going Beyond r2
A Hopping Center of Action
A Leap
A Couple of General Reflections
Conclusions
QUANTUM-CHEMICAL DESCRIPTORS IN QSAR/QSPR MODELING: ACHIEVEMENTS, PERSPECTIVES AND TRENDS
Introduction
Quantum-Chemical Methods and Descriptors
Computational Approaches for Establishing Quantitative Structure-Activity Relationships
Quantum-Chemical Descriptors in QSAR/QSPR Models
Summary and Conclusions
PLATINUM COMPLEXES AS ANTI-CANCER DRUGS: MODELING OF STRUCTURE, ACTIVATION AND FUNCTION
Introduction to Cisplatin Chemistry and Biochemistry
Calculation of Cisplatin Structure, Activation and DNA Interactions
Platinum-Based Alternatives
Non-Platinum Alternatives
Absorption, Distribution, Metabolism, Excretion (ADME) Aspects
PROTEIN MISFOLDING: THE QUANTUM BIOCHEMICAL SEARCH FOR A SOLUTION TO ALZHEIMER'S DISEASE
Introduction
Protein Folding and Misfolding
Quantum Biochemistry in the Study of Protein Misfolding
Alzheimer's Disease: A Disorder of Protein Misfolding
Quantum Biochemistry and Designing Drugs for Alzheimer's Disease
Conclusions
TARGETING BUTYRYLCHOLINESTERASE FOR ALZHEIMER'S DISEASE THERAPY
Butyrylcholinesterase and the Regulation of Cholinergic Neurotransmission
Butyrylcholinesterase: The Significant other Cholinesterase, in Sickness and in Health
Optimizing Specific Inhibitors of Butyrylcholinesterase Based on the Phenothiazine Scaffold
Biological Evaluation of Phenothiazine Derivatives as Cholinesterase Inhibitors
Computation of Physical Parameters to Interpret Structure-Activity Relationships
Enzyme-Inhibitor Structure-Activity Relationships
Conclusions
REDUCTION POTENTIALS OF PEPTIDE-BOUND COPPER(II) - RELEVANCE FOR ALZHEIMER'S DISEASE AND PRION DISEASES
Introduction
Copper Binding in Albumin - Type 2
Copper Binding to Ceruloplasmin - Type 1
The Prion Protein Octarepeat Region
Copper and the Amyloid Beta Peptide (AAlpha) of Alzheimer's Disease
Cu(II)/Cu(I) Reduction Potentials in Cu/AAlpha
Concluding Remarks
Appendix
THEORETICAL INVESTIGATION OF NSAID PHOTODEGRADATION MECHANISMS
Drug Safety
Drug Photosensitivity
Non-Steroid Anti-Inflammatory Drugs (NSAIDs)
NSAID Phototoxicity
Theoretical Studies
Redox Chemistry
NSAID Orbital Structures
NSAID Absorption Spectra
Excited State Reactions
Reactive Oxygen Species (ROS) and Radical Formation
Effects of the Formed ROS and Radicals during the Photodegradation Mechanisms
Conclusions

PART V: Biochemical Signature of Quantum Indeterminism

QUANTUM INDETERMINISM, MUTATION, NATURAL SELECTION, AND THE MEANING OF LIFE
Introduction
A Short History of the Debate in Philosophy of Biology
Replies to My Paper
The Quantum Indeterministic Basis of Mutations
Mutation and the Direction of Evolution
Mutational Order
The Nature of Natural Selection
The Meaning of Life
MOLECULAR ORBITALS: DISPOSITIONS OR PREDICTIVE STRUCTURES?
Origins of Quantum Models in Chemistry: The Composite and the Aggregate
Evolution of the Quantum Approaches and Biology
Philosophical Implications of Molecular Quantum Holism: Dispositions and Predictive Structures
Closing Remarks