Quantum Biochemistry, 2 Teile

DNA Base-Gold InteractionInteraction of Watson-Crick DNA Base Pairs with Gold ClustersSummary and PerspectivesQUANTUM MECHANICAL STUDIES OF NONCOVALENT DNA-PROTEIN INTERACTIONSIntroductionComputational Approaches for Studying Noncovalent InteractionsHydrogen-Bonding InteractionsInteractions between Aromatic DNA-Protein ComponentsCation-pi Interactions between DNA-Protein ComponentsConclusionsTHE VIRIAL FIELD AND TRANSFERABILITY IN DNA BASE-PAIRINGA New Theorem Relating the Density of an Atom in a Molecule to the EnergyComputationsChemical Transferability and the One-Electron Density MatrixChanges in Atomic Energies Encountered in DNA Base PairingEnergy Changes in the WC Pairs GC and ATDiscussionAN ELECTRON DENSITY-BASED APPROACH TO THE ORIGIN OF STACKING INTERACTIONSIntroductionComputational MethodCharge-Transfer Complexes: Quinhydronepi-pi Interactions in Hetero-Molecular Complexes: Methyl Gallate-Caffeine Adductpi-pi Interactions between DNA Base Pair Stepspi-pi Interactions in Homo-Molecular Complexes: CatecholC-H/pi ComplexesProvisional Conclusions and Future ResearchPOLARIZABILITIES OF AMINO ACIDS: ADDITIVE MODELS AND AB INITIO CALCULATIONSIntroductionModels of PolarizabilityPolarizabilities of the Amino AcidsConcluding RemarksMETHODS IN BIOCOMPUTATIONAL CHEMISTRY: A LESSON FROM THE AMINO ACIDSIntroductionConformers, Rotamers and Physicochemical VariablesQTAIM Side Chain Polarizations and the Theoretical Classification of Amino AcidsQuantum Mechanical Studies of Peptide-Host InteractionsConclusionsFROM ATOMS IN AMINO ACIDS TO THE GENETIC CODE AND PROTEIN STABILITY, AND BACKWARDSContext of the WorkThe Electron Density rho(r) as an Indirectly Measurable Dirac ObservableBrief Review of Some Basic Concepts of the Quantum Theory of Atoms in MoleculesComputational Approach and Level of TheoryEmpirical Correlations of QTAIM Atomic Properties of Amino Acid Side Chains with ExperimentMolecular ComplementarityClosing RemarksAppendix A: X-Ray and Neutron Diffraction Geometries of the Amino Acids in the LiteratureENERGY RICHNESS OF ATP IN TERMS OF ATOMIC ENERGIES: A FIRST STEPIntroductionHow "(De)Localized" is the Enthalpy of Bond Dissociation?The Choice of a Theoretical LevelComputational 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+ConclusionsVOLUME TWOPART III: Reactivity, Enzyme Catalysis, Biochemical Reaction Paths and MechanismsQUANTUM TRANSITION STATE FOR PEPTIDE BOND FORMATION IN THE RIBOSOMEIntroductionMethodology: Searching for the Transition State and Calculating its PropertiesResults: The Quantum Mechanical Transition StateDiscussionSummary and ConclusionsHYBRID QM/MM SIMULATIONS OF ENZYME-CATALYZED DNA REPAIR REACTIONSIntroductionTheoretical BackgroundApplicationsConclusionsCOMPUTATIONAL ELECTRONIC STRUCTURE OF SPIN-COUPLED DIIRON-OXO PROTEINSIntroduction(Anti)ferromagnetic Spin CouplingSpin Density Functional Theory of Antiferromagnetic Diiron ComplexesPhenomenological Simulation of Mössbauer Spectra of Diiron-Oxo ProteinsConclusionACCURATE DESCRIPTION OF SPIN STATES AND ITS IMPLICATIONS FOR CATALYSISIntroductionInfluence of the Basis SetSpin-Contamination CorrectionsInfluence of Self-ConsistencySpin-States of Model ComplexesSpin-States Involved in Catalytic CyclesConcluding RemarksComputational DetailsQUANTUM MECHANICAL APPROACHES TO SELENIUM BIOCHEMISTRYIntroductionQuantum Mechanical Methods for the Treatment of SeleniumApplications to Selenium BiochemistrySummaryCATALYTIC MECHANISM OF METALLO BETA-LACTAMASES: INSIGHTS FROM CALCULATIONS AND EXPERIMENTSIntroductionStructural InformationComputational DetailsPreliminary Comment on the Comparison between Theory and ExperimentMichaelis Complex in B1 MBetaLsCatalytic Mechanism of B1 MBetaLsMichaelis Complexes of other MBetaLsConcluding RemarksCOMPUTATIONAL SIMULATION OF THE TERMINAL BIOGENESIS OF SESQUITERPENES: THE CASE OF 8-EPICONFERTINIntroductionReaction MechanismConclusionsMECHANISTICS OF ENZYME CATALYSIS: FROM SMALL TO LARGE ACTIVE-STIE MODELSIntroductionActive-Site Models of Enzymatic Catalysis: Methods and AccuracyRedox Catalytic MechanismsGeneral Acid-Base Catalytic Mechanism of Deacetylation in LpxCSummaryPART IV: From Quantum Biochemistry to Quantum Pharmacology, Therapeutics, and Drug DesignDEVELOPING QUANTUM TOPOLOGICAL MOLECULAR SIMILARITY (QTMS)IntroductionAnchoring in Physical Organic ChemistryEquilibrium Bond Lengths: "Threat" or "Opportunity"?Introducing Chemometrics: Going Beyond r2A Hopping Center of ActionA LeapA Couple of General ReflectionsConclusionsQUANTUM-CHEMICAL DESCRIPTORS IN QSAR/QSPR MODELING: ACHIEVEMENTS, PERSPECTIVES AND TRENDSIntroductionQuantum-Chemical Methods and DescriptorsComputational Approaches for Establishing Quantitative Structure-Activity RelationshipsQuantum-Chemical Descriptors in QSAR/QSPR ModelsSummary and ConclusionsPLATINUM COMPLEXES AS ANTI-CANCER DRUGS: MODELING OF STRUCTURE, ACTIVATION AND FUNCTIONIntroduction to Cisplatin Chemistry and BiochemistryCalculation of Cisplatin Structure, Activation and DNA InteractionsPlatinum-Based AlternativesNon-Platinum AlternativesAbsorption, Distribution, Metabolism, Excretion (ADME) AspectsPROTEIN MISFOLDING: THE QUANTUM BIOCHEMICAL SEARCH FOR A SOLUTION TO ALZHEIMER'S DISEASEIntroductionProtein Folding and MisfoldingQuantum Biochemistry in the Study of Protein MisfoldingAlzheimer's Disease: A Disorder of Protein MisfoldingQuantum Biochemistry and Designing Drugs for Alzheimer's DiseaseConclusionsTARGETING BUTYRYLCHOLINESTERASE FOR ALZHEIMER'S DISEASE THERAPYButyrylcholinesterase and the Regulation of Cholinergic NeurotransmissionButyrylcholinesterase: The Significant other Cholinesterase, in Sickness and in HealthOptimizing Specific Inhibitors of Butyrylcholinesterase Based on the Phenothiazine ScaffoldBiological Evaluation of Phenothiazine Derivatives as Cholinesterase InhibitorsComputation of Physical Parameters to Interpret Structure-Activity RelationshipsEnzyme-Inhibitor Structure-Activity RelationshipsConclusionsREDUCTION POTENTIALS OF PEPTIDE-BOUND COPPER(II) - RELEVANCE FOR ALZHEIMER'S DISEASE AND PRION DISEASESIntroductionCopper Binding in Albumin - Type 2Copper Binding to Ceruloplasmin - Type 1The Prion Protein Octarepeat RegionCopper and the Amyloid Beta Peptide (AAlpha) of Alzheimer's DiseaseCu(II)/Cu(I) Reduction Potentials in Cu/AAlphaConcluding RemarksAppendixTHEORETICAL INVESTIGATION OF NSAID PHOTODEGRADATION MECHANISMSDrug SafetyDrug PhotosensitivityNon-Steroid Anti-Inflammatory Drugs (NSAIDs)NSAID PhototoxicityTheoretical StudiesRedox ChemistryNSAID Orbital StructuresNSAID Absorption SpectraExcited State ReactionsReactive Oxygen Species (ROS) and Radical FormationEffects of the Formed ROS and Radicals during the Photodegradation MechanismsConclusionsPART V: Biochemical Signature of Quantum IndeterminismQUANTUM INDETERMINISM, MUTATION, NATURAL SELECTION, AND THE MEANING OF LIFEIntroductionA Short History of the Debate in Philosophy of BiologyReplies to My PaperThe Quantum Indeterministic Basis of MutationsMutation and the Direction of EvolutionMutational OrderThe Nature of Natural SelectionThe Meaning of LifeMOLECULAR ORBITALS: DISPOSITIONS OR PREDICTIVE STRUCTURES?Origins of Quantum Models in Chemistry: The Composite and the AggregateEvolution of the Quantum Approaches and BiologyPhilosophical Implications of Molecular Quantum Holism: Dispositions and Predictive StructuresClosing Remarks