Quantum Biochemistry

Quantum Biochemistry......Page 2
Acknowledgment......Page 10
Congratulations to Professor Ada Yonath for Winning the 2009 Nobel Prize in Chemistry......Page 12
Introductory Reflections on Quantum Biochemistry: From Context to Contents......Page 14
Contents......Page 38
List of Contributors......Page 54
Part One Novel Theoretical, Computational, and Experimental Methods and Techniques......Page 62
1.1 Introduction......Page 64
1.2.1 General Problem of N-Representability......Page 65
1.2.2 Single Determinant N-Representability......Page 66
1.2.3.1 Beryllium......Page 68
1.2.3.2 Maleic Anhydride......Page 70
1.3.1 Computational Difficulty of Large Molecules......Page 71
1.3.2 Quantum Kernel Formalism......Page 72
1.3.3 Kernel Matrices: Example and Results......Page 75
1.3.4.1 Hydrated Hexapeptide Molecule......Page 78
1.3.4.2 Hydrated Leu1-Zervamicin......Page 79
1.4 Kernel Density Matrices Led to Kernel Energies......Page 83
1.4.1 KEM Applied to Peptides......Page 85
1.4.2 Quantum Models within KEM......Page 90
1.4.2.1 Calculations and Results Using Different Basis Functions for the ADPGV7b Molecule......Page 93
1.4.2.2 Calculations and Results Using Different Quantum Methods for the Zaib4 Molecule......Page 95
1.4.3.1 KEM Calculation Results......Page 97
1.4.3.2 Comments Regarding the Insulin Calculations......Page 99
1.4.4.1 KEM Calculation Results......Page 100
1.4.5 KEM Applied to tRNA......Page 102
1.4.6.1 Importance of the Interaction Energy for Rational Drug Design......Page 104
1.4.6.2 Sample Calculation: Antibiotic Drug in Complex (1O9M) with a Model Aminoacyl Site of the 30s Ribosomal Subunit......Page 105
1.4.6.3 Comments Regarding the Drug–Target Interaction Calculations......Page 107
1.4.7.2 Collagen 1A89......Page 108
1.4.8.1 Molecular Energy as a Sum over Kernel Energies......Page 111
1.4.8.2 Application to Leu1-zervamicin of the Fourth-Order Approximation of KEM......Page 112
1.4.9.1 Vesicular Stomatitis Virus Nucleoprotein (2QVJ) Molecule......Page 114
1.4.9.3 Comments regarding the 2QVJ Calculations......Page 115
1.5 Summary and Conclusions......Page 116
References......Page 118
2.1 Introduction......Page 122
2.2 QM/MM......Page 123
2.3 ONIOM......Page 124
2.4 Guidelines for the Application of ONIOM......Page 126
2.5 The Cancellation Problem......Page 133
2.6 Use of Point Charges......Page 138
2.7 Conclusions......Page 142
References......Page 143
3.1 Introduction......Page 146
3.2.1 Quantum Mechanical (QM) Methods......Page 147
3.2.3 QM/MM Methods......Page 149
3.2.4 QM/MM Model and Setup......Page 151
3.3.1.1 Binding and Photodissociation of Diatomic Molecules......Page 152
3.3.1.2 Heme Oxygenase (HO)......Page 156
3.3.1.3 Indoleamines Dioxygenase (IDO) and Tryptophan Dioxygenase (TDO)......Page 158
3.3.1.4 Nitric Oxide Synthase (NOS)......Page 162
3.3.2.1 Methylmalonyl-CoA Mutase......Page 166
3.3.2.2 Glutamine Mutase......Page 169
3.4.1 Fluorescent Proteins (FPs)......Page 170
3.4.1.1 Green Fluorescent Proteins (GFP)......Page 171
3.4.1.2 Reversible Photoswitching Fluorescent Proteins (RPFPs)......Page 172
3.4.1.3 Photoconversion of Fluorescent Proteins......Page 176
3.4.2 Luciferases......Page 178
References......Page 181
4.1 Introduction......Page 192
4.2.1 Molecular Electrostatic Potential......Page 193
4.2.1.2 Semiclassical Approximation......Page 194
4.2.1.3 MEP as a Component of the Intermolecular Interaction......Page 195
4.2.1.5 Simplifications in the Expression of Ees: Point Charge Descriptions......Page 196
4.2.1.7 Simplifications in the Expression of Ees: Multipolar Expansions......Page 197
4.2.2 Interaction Energy between Two Molecules......Page 198
4.2.3.2 Interactions with Other Cations......Page 200
4.2.4 Interaction Potentials (Force Fields) for Computer Simulations of Liquid Systems......Page 201
4.3.1 Basic Formulation of PCM......Page 203
4.3.2.1 Dielectric Function......Page 207
4.3.2.4 Description of the Solute......Page 208
4.3.3.1 Apparent Surface Charge (ASC) Methods......Page 209
4.3.3.3 Generalized Born Model......Page 210
4.4.1 Solvation Energies......Page 211
4.4.3 Chemical Equilibria......Page 213
4.4.3.3 pKa of Acids......Page 214
4.4.4 Reaction Mechanisms......Page 215
4.4.5 Solvent Effects on Molecular Properties and Spectroscopy......Page 217
4.4.5.1 N-Acetylproline Amide (NAP)......Page 218
4.4.5.2 Glucose......Page 219
4.4.5.3 Local Field Effects......Page 220
4.4.5.4 Dynamic Effects......Page 221
4.4.6 Effect of the Environment on Formation and Relaxation of Excited States......Page 222
4.4.7 Electronic Transitions and Related Spectroscopies......Page 223
4.4.8 Photoinduced Electron and Energy Transfers......Page 225
References......Page 227
5.1 Motivation......Page 232
5.2.2 Two End Methods......Page 233
5.2.3 Surface Walking Algorithms......Page 234
5.2.5 Fast Marching Method......Page 235
5.3.1 Introduction to FMM......Page 236
5.3.3 Heapsort Technique......Page 237
5.3.4 Shepard Interpolation......Page 238
5.3.5 Interpolating Moving Least-Squares Method......Page 240
5.3.6.1 Setup, Definitions and Notation......Page 241
5.3.6.4 Backtracing from the Ending Point to the Starting Point on the Energy Cost......Page 242
5.3.7.1 Four-Well Analytical PES......Page 243
5.3.7.2 SN2 Reaction [31]......Page 245
5.3.7.3 Dissociation of Ionized O-Methylhydroxylamine [31]......Page 246
5.4.1 QM/MM Methods......Page 248
5.4.2 Incorporating the QM/MM-MFEP Methods with FMM......Page 250
5.4.3.2 Isomerization Reaction Catalyzed by 4-Oxalocrotonate......Page 251
5.5 Summary......Page 252
References......Page 253
Part Two Nucleic Acids, Amino Acids, Peptides and Their Interactions......Page 258
6.1.1 Prebiotic Chemistry: Experimental Endeavor to Synthesize the Building Blocks of Biopolymers......Page 260
6.1.2 Key Role of HCN as a Precursor for Prebiotic Compounds......Page 262
6.2 Computational Investigation......Page 263
6.2.2 Thermochemistry of Pentamerization......Page 265
6.2.3.2 Is an Anionic Mechanism Feasible in Isolation?......Page 266
6.2.3.3 Two Tautomeric forms of AICN: Which one is the Favorable Precursor for Adenine Formation under Prebiotic Conditions?......Page 268
6.3 Conclusion......Page 274
References......Page 277
7.1 Introduction......Page 280
7.2 Methodological Aspects......Page 281
7.3 Ionization of DNA Base Pairs......Page 282
7.3.1 Equilibrium Geometries and Dimerization Energies......Page 283
7.3.2 Single and Double Proton Transfer Reactions......Page 284
7.4.1 Structural Features of Neutral and Radical Cation Amino Acids......Page 288
7.4.2 Intramolecular Proton-Transfer Processes......Page 292
7.5.1 Ionization of N-Glycylglycine......Page 295
7.5.2 Influence of Ionization on the Ramachandran Maps of Model Peptides......Page 297
7.6 Conclusions......Page 300
References......Page 302
8.1 Introductory Nanoscience Background......Page 306
8.1.1 Gold in Nanodimensions......Page 307
8.1.2 Gold and DNA: Meeting Points in Nanodimensions......Page 309
8.2 DNA–Gold Bonding Patterns: Some Experimental Facts......Page 314
8.3.1 Adenine–Au and Adenine–Au3 Bonding Patterns......Page 315
8.3.2 Propensity of Gold to Act as Nonconventional Proton Acceptor......Page 318
8.3.2.1 Pause: A Short Excursion to Hydrogen Bonding Theory......Page 320
8.3.2.2 Proof that N H [ Au : N–H      Au in A Au3(Ni¼1,3,7)......Page 321
8.3.2.3 Nonconventional Hydrogen Bonds N H      Au in A Au3 (Ni¼1,3,7)......Page 322
8.3.4 Interaction between Adenine and Chain Au3 Cluster......Page 323
8.4 Guanine–Gold Interaction......Page 324
8.5 Thymine–Gold Interactions......Page 329
8.6 Cytosine–Gold Interactions......Page 333
8.7 Basic Trends of DNA Base–Gold Interaction......Page 334
8.7.1 Anchoring Bond in DNA Base–Gold Complexes......Page 337
8.7.2 Energetics in Z = 0 Charge State......Page 339
8.7.3 Z =  -1 Charge State......Page 343
8.8.1 General Background......Page 347
8.8.2 [A T] Au3 Complexes......Page 350
8.8.3 [G C] Au3 Complexes......Page 354
8.8.4 Au6 Cluster Bridges the WC G C Pair......Page 357
8.9 Summary and Perspectives......Page 358
References......Page 359
9.1 Introduction......Page 368
9.2 Computational Approaches for Studying Noncovalent Interactions......Page 369
9.3.1 Interactions between the Protein Backbone and DNA Nucleobases......Page 376
9.3.2 Interactions between Protein Side Chains and DNA Backbone......Page 377
9.3.3 Interactions between Protein Side Chains and DNA Nucleobases......Page 378
9.4 Interactions between Aromatic DNA–Protein Components......Page 379
9.4.1 Stacking Interactions......Page 380
9.4.2 T-Shaped Interactions......Page 384
9.5.1 Cation–p Interactions between Charged Nucleobases and Aromatic Amino Acids......Page 387
9.5.3 Cation–p Interactions Involving Charged Non-aromatic Amino Acids......Page 391
9.5.4 Simultaneous Cation–p and Hydrogen-Bonding Interactions (DNA–Protein Stair Motifs)......Page 393
References......Page 394
10.1 A New Theorem Relating the Density of an Atom in a Molecule to the Energy......Page 398
10.3 Chemical Transferability and the One-Electron Density Matrix......Page 400
10.3.1 The Virial Field......Page 401
10.3.2 Short-Range Nature of the Virial Field and Transferability......Page 403
10.4 Changes in Atomic Energies Encountered in DNA Base Pairing......Page 404
10.4.1 Dimerization of the Four Bases A, C, G and T......Page 407
10.4.3 Energy Changes in AA1......Page 410
10.5 Energy Changes in the WC Pairs GC and AT......Page 411
10.6 Discussion......Page 416
10.6.1 Attractive and Repulsive Contributions to the Atomic Virial and its Short-Range Nature......Page 417
10.6.2 Can One Go Directly to the Virial Field?......Page 421
References......Page 424
11.1 Introduction......Page 426
11.2 Computational Method......Page 427
11.3 Charge-Transfer Complexes: Quinhydrone......Page 428
11.4 p–p Interactions in Hetero-Molecular Complexes: Methyl Gallate–Caffeine Adduct......Page 432
11.5 p–p Interactions between DNA Base Pair Steps......Page 435
11.6 p–p Interactions in Homo-Molecular Complexes: Catechol......Page 439
11.7 C H/p Complexes......Page 442
References......Page 446
12.2 Models of Polarizability......Page 450
12.3 Polarizabilities of the Amino Acids......Page 454
12.4 Concluding Remarks......Page 459
References......Page 461
13.1 Introduction......Page 464
13.2 Conformers, Rotamers and Physicochemical Variables......Page 465
13.3 QTAIM Side Chain Polarizations and the Theoretical Classification of Amino Acids......Page 469
13.4 Quantum Mechanical Studies of Peptide–Host Interactions......Page 475
13.5 Conclusions......Page 480
References......Page 481
14.1 Context of the Work......Page 484
14.2 The Electron Density r(r) as an Indirectly Measurable Dirac Observable......Page 487
14.3 Brief Review of Some Basic Concepts of the Quantum Theory of Atoms in Molecules......Page 491
14.4 Computational Approach and Level of Theory......Page 499
14.5.1 Partial Molar Volumes......Page 500
14.5.3 Simulation of Genetic Mutations with Amino Acids Partition Coefficients......Page 509
14.5.4 Effect of Genetic Mutation on Protein Stability......Page 512
14.5.5 From the Genetic Code to the Density and Back......Page 515
14.6 Molecular Complementarity8)......Page 517
14.8 Appendix A X-Ray and Neutron Diffraction Geometries of the Amino Acids in the Literature9)......Page 523
References......Page 528
15.1 Introduction......Page 534
15.2 How .(De)Localized. is the Enthalpy of Bond Dissociation?......Page 535
15.3.1 The Problem......Page 538
15.3.3.1 QTAIM Atomic Energies from the ab initio Methods......Page 539
15.3.3.2 Atomic Energies from Kohn–Sham Density Functional Theory Methods......Page 543
15.4 Computational Details......Page 545
15.6.1 Phosphate Group Energies and Modified Lipmann.s Group Transfer Potentials......Page 546
15.7.1 Bond Properties and Molecular Graphs......Page 548
15.7.2 Group Charges in ATP in the Absence and Presence of Mg2þ......Page 552
15.7.3 Molecular Electrostatic Potential in the Absence and Presence of Mg2þ......Page 553
15.8 Conclusions......Page 554
References......Page 557
Part Three Reactivity, Enzyme Catalysis, Biochemical Reaction Paths and Mechanisms......Page 560
16.1 Introduction......Page 562
16.2 Methodology: Searching for the Transition State and Calculating its Properties......Page 563
16.3 Results: The Quantum Mechanical Transition State......Page 567
16.4 Discussion......Page 572
16.5 Summary and Conclusions......Page 574
References......Page 575
17.1 Introduction......Page 578
17.2 Theoretical Background......Page 579
17.3.1 Thymine Dimer Splitting Catalyzed by DNA Photolyase......Page 582
17.3.2 Reaction Mechanism of Endonuclease IV......Page 586
17.3.3 Role of Water in the Catalysis Mechanism of DNA Repair Enzyme, MutY......Page 590
17.4 Conclusions......Page 594
References......Page 595
18.1 Introduction......Page 598
18.2 (Anti)ferromagnetic Spin Coupling......Page 599
18.3 Spin Density Functional Theory of Antiferromagnetic Diiron Complexes......Page 600
18.4.1 Antiferromagnetic Diiron Center of Hemerythrin......Page 603
18.4.2 Nitric Oxide Derivative of Hr......Page 604
18.4.3 Antiferromagnetic Diiron Center of Reduced Uteroferrin......Page 606
18.5 Conclusion......Page 607
References......Page 609
19.1 Introduction......Page 612
19.2 Influence of the Basis Set......Page 614
19.3 Spin-Contamination Corrections......Page 617
19.4 Influence of Self-Consistency......Page 619
19.5 Spin-States of Model Complexes......Page 620
19.6.1 Cytochrome P450cam......Page 625
19.6.2 His-Porphyrin Models......Page 628
19.6.2.1 Reference Data (Harvey)......Page 629
19.6.2.2 Reference Data (Ghosh)......Page 631
19.6.2.3 Other Model Systems......Page 632
19.6.3 NiFe Hydrogenase......Page 635
19.8 Computational Details......Page 640
References......Page 641
20.1 Introduction......Page 646
20.2 Quantum Mechanical Methods for the Treatment of Selenium......Page 647
20.3.1 Computational Studies of GPx......Page 648
20.3.2.1 GPx-like Activity of Ebselen......Page 650
20.3.2.2 Substituent Effects on the GPx-like Activity of Ebselen......Page 657
20.3.2.3 Effect of the Molecular Environment on GPx-like Activity......Page 659
References......Page 661
21.1 Introduction......Page 666
21.2 Structural Information......Page 668
21.3 Computational Details......Page 669
21.4 Preliminary Comment on the Comparison between Theory and Experiment......Page 670
21.5.1 Substrate Binding Determinants......Page 671
21.5.2 Nucleophile Structural Determinants......Page 672
21.6 Catalytic Mechanism of B1 MbLs......Page 673
21.6.1 Cefotaxime Enzymatic Hydrolysis in CcrA [56]......Page 674
21.6.2 Cefotaxime Enzymatic Hydrolysis in BcII [53]......Page 675
21.6.4 Reactivity of b-Lactam Antibiotics other than Cefotaxime......Page 676
21.7.2 B3 MbL Subclass......Page 677
21.8 Concluding Remarks......Page 678
References......Page 679
22.1 Introduction......Page 684
22.2 Reaction Mechanism......Page 688
22.3 Conclusions......Page 700
References......Page 701
23.1.1 Factors Influencing the Catalytic Performance of Enzymes......Page 704
23.1.2 Computational Modeling in Enzymology......Page 709
23.2 Active-Site Models of Enzymatic Catalysis: Methods and Accuracy......Page 711
23.3.1 NO Formation in Nitric Oxide Synthase......Page 713
23.3.2 Oxidative Dealkylation in the AlkB Family......Page 715
23.4 General Acid–Base Catalytic Mechanism of Deacetylation in LpxC......Page 719
23.5 Summary......Page 721
References......Page 723
Part Four From Quantum Biochemistry to Quantum Pharmacology, Therapeutics, and Drug Design......Page 728
24.1 Introduction......Page 730
24.2 Anchoring in Physical Organic Chemistry......Page 732
24.3 Equilibrium Bond Lengths: .Threat. or .Opportunity.?......Page 739
24.4 Introducing Chemometrics: Going Beyond r2......Page 740
24.5 A Hopping Center of Action......Page 742
24.6 A Leap......Page 745
24.7 A Couple of General Reflections......Page 748
24.8 Conclusions......Page 749
References......Page 750
25.1 Introduction......Page 754
25.2.1 Quantum-Chemical Methods......Page 755
25.2.2 Quantum-Chemical Descriptors: Classification, Updates......Page 758
25.3.1 Selection of Descriptors......Page 764
25.3.2 Linear Regression Techniques......Page 766
25.3.3 Machine-Learning Algorithms......Page 767
25.4.1 Biochemistry and Molecular Biology......Page 771
25.4.2 Medicinal Chemistry and Drug Design......Page 773
25.4.3 Material and Biomaterial Science......Page 775
25.5 Summary and Conclusions......Page 776
References......Page 778
26.1 Introduction to Cisplatin Chemistry and Biochemistry......Page 784
26.2 Calculation of Cisplatin Structure, Activation and DNA Interactions......Page 787
26.3 Platinum-Based Alternatives......Page 793
26.4 Non-platinum Alternatives......Page 796
26.5 Absorption, Distribution, Metabolism, Excretion (ADME) Aspects......Page 800
References......Page 801
27.1 Introduction......Page 804
27.2.1 Protein Folding......Page 805
27.3 Quantum Biochemistry in the Study of Protein Misfolding......Page 806
27.3.1 Molecular Mechanics......Page 807
27.4 Alzheimer.s Disease: A Disorder of Protein Misfolding......Page 808
27.4.2 Protein Misfolding of Beta-Amyloid......Page 809
27.5 Quantum Biochemistry and Designing Drugs for Alzheimer.s Disease......Page 811
27.5.1 Approach 1 – Homotaurine......Page 812
27.5.2 Approach 2 – Melatonin......Page 813
27.6 Conclusions......Page 814
References......Page 815
28.1 Butyrylcholinesterase and the Regulation of Cholinergic Neurotransmission......Page 818
28.2 Butyrylcholinesterase: The Significant other Cholinesterase, in Sickness and in Health......Page 821
28.4 Biological Evaluation of Phenothiazine Derivatives as Cholinesterase Inhibitors......Page 822
28.5 Computation of Physical Parameters to Interpret Structure–Activity Relationships......Page 830
28.6 Enzyme–Inhibitor Structure–Activity Relationships......Page 833
28.7 Conclusions......Page 838
References......Page 839
29.1 Introduction......Page 842
29.2 Copper Binding in Albumin – Type 2......Page 844
29.3 Copper Binding to Ceruloplasmin – Type 1......Page 846
29.4 The Prion Protein Octarepeat Region......Page 848
29.5 Copper and the Amyloid Beta Peptide (Ab) of Alzheimer.s Disease......Page 850
29.6 Cu(II)/Cu(I) Reduction Potentials in Cu/Ab......Page 852
29.7 Concluding Remarks......Page 855
29.A.1 Calculation of Reduction Potentials, E , of Copper/Peptide Complexes......Page 856
29.A.2 Computational Methodology......Page 857
References......Page 859
30.1 Drug Safety......Page 866
30.2 Drug Photosensitivity......Page 867
30.2.3 Phototoxicity......Page 868
30.3.2 Pharmacological Action......Page 869
30.3.3 NSAID Uses......Page 870
30.3.4 Side Effects......Page 871
30.4 NSAID Phototoxicity......Page 872
30.5.1 Overview......Page 873
30.5.2 Methodology......Page 875
30.6 Redox Chemistry......Page 876
30.7 NSAID Orbital Structures......Page 878
30.8 NSAID Absorption Spectra......Page 881
30.9 Excited State Reactions......Page 884
30.9.1 Photodegradation from the T1 State......Page 886
30.9.2 Possible Photodegradation from Singlet Excited States......Page 887
30.10 Reactive Oxygen Species (ROS) and Radical Formation......Page 888
30.11 Effects of the Formed ROS and Radicals during the Photodegradation Mechanisms......Page 889
30.12 Conclusions......Page 891
References......Page 892
Part Five Biochemical Signature of Quantum Indeterminism......Page 896
31.1 Introduction......Page 898
31.2 A Short History of the Debate in Philosophy of Biology......Page 900
31.3 Replies to My Paper......Page 903
31.4.1 Tautomeric Shifts......Page 906
31.4.2 Proton Tunneling......Page 910
31.4.3 Aqueous Thermal Motion......Page 913
31.5 Mutation and the Direction of Evolution......Page 914
31.6 Mutational Order......Page 916
31.7 The Nature of Natural Selection......Page 918
31.8 The Meaning of Life......Page 924
References......Page 928
32 Molecular Orbitals: Dispositions or Predictive Structures?......Page 934
32.1 Origins of Quantum Models in Chemistry: The Composite and the Aggregate......Page 936
32.2 Evolution of the Quantum Approaches and Biology......Page 937
32.3.1 Molecular Landscapes and Process......Page 943
32.3.2 Realism of Disposition and Predictive Structures......Page 947
References......Page 954
Index......Page 958