MOLECULAR MODELLING PRINCIPLES AND APPLICATIONS SECOND EDITIONPDF|Epub|txt|kindle电子书版本网盘下载

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1 Useful Concepts in Molecular Modelling1

1.1 Introduction1

1.2 Coordinate Systems2

1.3 Potential Energy Surfaces4

1.4 Molecular Graphics5

1.5 Surfaces6

1.6 Computer Hardware and Software8

1.7 Units of Length and Energy9

1.8 The Molecular Modelling Literature9

1.9 The Internet9

1.10 Mathematical Concepts10

Further Reading24

References24

2 An Introduction to Computational Quantum Mechanics26

2.1 Introduction26

2.2 One-electron Atoms30

2.3 Polyelectronic Atoms and Molecules34

2.4 Molecular Orbital Calculations41

2.5 The Hartree-Fock Equations51

2.6 Basis Sets65

2.7 Calculating Molecular Properties Using ab initio Quantum Mechanics74

2.8 Approximate Molecular Orbital Theories86

2.9 Semi-empirical Methods86

2.10 Hückel Theory99

2.11 Performance of Semi-empirical Methods102

Appendix 2.1 Some Common Acronyms Used in Computational Quantum Chemistry104

Further Reading105

References105

3 Advanced ab initio Methods， Density Functional Theory and Solid-state Quantum Mechanics108

3.1 Introduction108

3.2 Open-shell Systems108

3.3 Electron Correlation110

3.4 Practical Considerations When Performing ab initio Calculations117

3.5 Energy Component Analysis122

3.6 Valence Bond Theories124

3.7 Density Functional Theory126

3.8 Quantum Mechanical Methods for Studying the Solid State138

3.9 The Future Role of Quantum Mechanics： Theory and Experiment Working Together160

Appendix 3.1 Alternative Expression for a Wavefunction Satisfying Bloch’s Function161

Further Reading161

References162

4 Empirical Force Field Models： Molecular Mechanics165

4.1 Introduction165

4.2 Some General Features of Molecular Mechanics Force Fields168

4.3 Bond Stretching170

4.4 Angle Bending173

4.5 Torsional Terms173

4.6 Improper Torsions and Out-of-plane Bending Motions176

4.7 Cross Terms： Class 1， 2 and 3 Force Fields178

4.8 Introduction to Non-bonded Interactions181

4.9 Electrostatic Interactions181

4.10 Van der Waals Interactions204

4.11 Many-body Effects in Empirical Potentials212

4.12 Effective Pair Potentials214

4.13 Hydrogen Bonding in Molecular Mechanics215

4.14 Force Field Models for the Simulation of Liquid Water216

4.15 United Atom Force Fields and Reduced Representations221

4.16 Derivatives of the Molecular Mechanics Energy Function225

4.17 Calculating Thermodynamic Properties Using a Force Field226

4.18 Force Field Parametrisation228

4.19 Transferability of Force Field Parameters231

4.20 The Treatment of Delocalised π Systems233

4.21 Force Fields for Inorganic Molecules234

4.22 Force Fields for Solid-state Systems236

4.23 Empirical Potentials for Metals and Semiconductors240

Appendix 4.1 The Interaction Between Two Drude Molecules246

Further Reading247

References247

5 Energy Minimisation and Related Methods for Exploring the Energy Surface253

5.1 Introduction253

5.2 Non-derivative Minimisation Methods258

5.3 Introduction to Derivative Minimisation Methods261

5.4 First-order Minimisation Methods262

5.5 Second Derivative Methods： The Newton-Raphson Method267

5.6 Quasi-Newton Methods268

5.7 Which Minimisation Method Should I Use？270

5.8 Applications of Energy Minimisation273

5.9 Determination of Transition Structures and Reaction Pathways279

5.10 Solid-state Systems： Lattice Statics and Lattice Dynamics295

Further Reading300

References301

6 Computer Simulation Methods303

6.1 Introduction303

6.2 Calculation of Simple Thermodynamic Properties307

6.3 Phase Space312

6.4 Practical Aspects of Computer Simulation315

6.5 Boundaries317

6.6 Monitoring the Equilibration321

6.7 Truncating the Potential and the Minimum Image Convention324

6.8 Long-range Forces334

6.9 Analysing the Results of a Simulation and Estimating Errors343

Appendix 6.1 Basic Statistical Mechanics347

Appendix 6.2 Heat Capacity and Energy Fluctuations348

Appendix 6.3 The Real Gas Contribution to the Virial349

Appendix 6.4 Translating Particle Back into Central Box for Three Box Shapes350

Further Reading351

References351

7 Molecular Dynamics Simulation Methods353

7.1 Introduction353

7.2 Molecular Dynamics Using Simple Models353

7.3 Molecular Dynamics with Continuous Potentials355

7.4 Setting up and Running a Molecular Dynamics Simulation364

7.5 Constraint Dynamics368

7.6 Time-dependent Properties374

7.7 Molecular Dynamics at Constant Temperature and Pressure382

7.8 Incorporating Solvent Effects into Molecular Dynamics： Potentials of Mean Force and Stochastic Dynamics387

7.9 Conformational Changes from Molecular Dynamics Simulations392

7.10 Molecular Dynamics Simulations of Chain Amphiphiles394

Appendix 7.1 Energy Conservation in Molecular Dynamics405

Further Reading406

References406

8 Monte Carlo Simulation Methods410

8.1 Introduction410

8.2 Calculating Properties by Integration412

8.3 Some Theoretical Background to the Metropolis Method414

8.4 Implementation of the Metropolis Monte Carlo Method417

8.5 Monte Carlo Simulation of Molecules420

8.6 Models Used in Monte Carlo Simulations of Polymers423

8.7 ’Biased’ Monte Carlo Methods432

8.8 Tackling the Problem of Quasi-ergodiciry： J-walking and Multicanonical Monte Carlo433

8.9 Monte Carlo Sampling from Different Ensembles438

8.10 Calculating the Chemical Potential442

8.11 The Configurational Bias Monte Carlo Method443

8.12 Simulating Phase Equilibria by the Gibbs Ensemble Monte Carlo Method450

8.13 Monte Carlo or Molecular Dynamics？452

Appendix 8.1 The Marsaglia Random Number Generator453

Further Reading454

References454

9 Conformational Analysis457

9.1 Introduction457

9.2 Systematic Methods for Exploring Conformational Space458

9.3 Model-building Approaches464

9.4 Random Search Methods465

9.5 Distance Geometry467

9.6 Exploring Conformational Space Using Simulation Methods475

9.7 Which Conformational Search Method Should I Use？ A Comparison of Different Approaches476

9.8 Variations on the Standard Methods477

9.9 Finding the Global Energy Minimum： Evolutionary Algorithms and Simulated Annealing479

9.10 Solving Protein Structures Using Restrained Molecular Dynamics and Simulated Annealing483

9.11 Structural Databases489

9.12 Molecular Fitting490

9.13 Clustering Algorithms and Pattern Recognition Techniques491

9.14 Reducing the Dimensionality of a Data Set497

9.15 Covering Conformational Space： Poling499

9.16 A ’Classic’ Optimisation Problem： Predicting Crystal Structures501

Further Reading505

References506

10 Protein Structure Prediction， Sequence Analysis and Protein Folding509

10.1 Introduction509

10.2 Some Basic Principles of Protein Structure513

10.3 First-principles Methods for Predicting Protein Structure517

10.4 Introduction to Comparative Modelling522

10.5 Sequence Alignment522

10.6 Constructing and Evaluating a Comparative Model539

10.7 Predicting Protein Structures by ’Threading’545

10.8 A Comparison of Protein Structure Prediction Methods： CASP547

10.9 Protein Folding and Unfolding549

Appendix 10.1 Some Common Abbreviations and Acronyms Used in Bioinformatics553

Appendix 10.2 Some of the Most Common Sequence and Structural Databases Used in Bioinformatics555

Appendix 10.3 Mutation Probability Matrix for 1 PAM556

Appendix 10.4 Mutation Probability Matrix for 250 PAM557

Further Reading557

References558

11 Four Challenges in Molecular Modelling： Free Energies， Solvation， Reactions and Solid-state Defects563

11.1 Free Energy Calculations563

11.2 The Calculation of Free Energy Differences564

11.3 Applications of Methods for Calculating Free Energy Differences569

11.4 The Calculation of Enthalpy and Entropy Differences574

11.5 Partitioning the Free Energy574

11.6 Potential Pitfalls with Free Energy Calculations577

11.7 Potentials of Mean Force580

11.8 Approximate/’Rapid’ Free Energy Methods585

11.9 Continuum Representations of the Solvent592

11.10 The Electrostatic Contribution to the Free Energy of Solvation：The Born and Onsager Models593

11.11 Non-electrostatic Contributions to the Solvation Free Energy608

11.12 Very Simple Solvation Models609

11.13 Modelling Chemical Reactions610

11.14 Modelling Solid-state Defects622

Appendix 11.1 Calculating Free Energy Differences Using Thermodynamic Integration630

Appendix 11.2 Using the Slow Growth Method for Calculating Free Energy Differences631

Appendix 11.3 Expansion of Zwanzig Expression for the Free Energy Difference for the Linear Response Method631

Further Reading632

References633

12 The Use of Molecular Modelling and Chemoinformatics to Discover and Design New Molecules640

12.1 Molecular Modelling in Drug Discovery640

12.2 Computer Representations of Molecules， Chemical Databases and 2D Substructure Searching642

12.3 3D Database Searching647

12.4 Deriving and Using Three-dimensional Pharmacophores648

12.5 Sources of Data for 3D Databases659

12.6 Molecular Docking661

12.7 Applications of 3D Database Searching and Docking667

12.8 Molecular Similarity and Similarity Searching668

12.9 Molecular Descriptors668

12.10 Selecting ’Diverse’ Sets of Compounds680

12.11 Structure-based De Novo Ligand Design687

12.12 Quantitative Structure-Activity Relationships695

12.13 Partial Least Squares706

12.14 Combinatorial Libraries711

Further Reading719

References720

Index727