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Combined quantum mechanical and molecular mechanical modelling of biomolecular interactions
- Author / Creator
- Available as
- Online
- Physical
Details
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- Creator
- Tatyana Karabencheva-Christova
- Format
- Books
- Language
- English
- Publication
-
- First edition
- Amsterdam, [Netherlands] : Academic Press, 2015
- ©2015
- Physical Details
-
- 1 online resource (0 p.)
- ISBNs
- 0128020032, 0128020180, 9780128020180, 9780128020036
- OCLC
- ocn925780014, ocn932329900, ocn911073447
- Description based upon print version of record.
- Includes bibliographical references at the end of each chapters and indexes.
- English
- Front Cover -- Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions -- Copyright -- Contents -- Contributors -- Preface -- Acknowledgments -- Chapter One: PUPIL: A Software Integration System for Multi-Scale QM/MM-MD Simulations and Its Application to Biomolecula ... -- 1. Introduction -- 2. QM/MM-MD Methodology -- 3. The PUPIL Framework -- 3.1. Features -- 3.1.1. High Performing Computing -- 3.2. User Interface -- 3.2.1. QM Program and Method Selection -- 3.2.2. QM Region Selection Rules -- 3.3. Technical Details -- 4. Biomolecular Applications -- 5. Recent Developments -- 5.1. Working with Multiple Active Zones -- 5.2. Treatment of Long-Range Electrostatic Interactions -- 6. Conclusions -- Acknowledgments -- References -- Chapter Two: Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorit... -- 1. Introduction -- 1.1. Free Energy Profiles of Enzymatic Reactions -- 1.1.1. MSMD and Jarzynski´s Relationship -- 1.1.2. Hybrid Differential Relaxation Algorithm -- 1.2. Mycobacterium tuberculosis Zinc Hydrolases -- 1.2.1. MshB (Rv1170) -- 1.2.2. MA-Amidase (Rv3717) -- 1.2.3. Zn Hydrolases Reaction Mechanism -- 2. Computational Methods -- 2.1. Theoretical Basis of HyDRA -- 2.2. Starting Structures -- 2.2.1. MshB -- 2.2.2. MA-Amidase -- 2.3. Classical, DFT, and QM/MM Simulation Parameters -- 2.4. Free Energy Determination Simulation Strategy and Parameters -- 2.4.1. Reaction Coordinate Definition -- 2.4.2. MSMD Trajectories and Pulling Speed -- 3. Results -- 3.1. Mtb Zinc Hydrolases Display a Flexible Zinc Coordination Sphere -- 3.2. Hydroxide Ion Generation Step -- 3.3. Hydroxide Attack to Amide Carbonyl -- 3.3.1. Effect of DRAr -- 3.3.2. Detailed Mechanistic and Comparative Analysis Between MshB and MA-Amidase -- 3.3.3. Role of Substrate Carbonyl Coordination
- 3.4. C-N Amide Bond Breaking -- 3.4.1. Stability of Tetrahedral Intermediate -- 3.4.2. FEPs of the C-N Bond Breaking Step -- 3.5. Alternative Mechanisms -- 4. Discussion -- 4.1. The Complete Mechanism of MshB and MA-Amidase Zn Hydrolases -- 4.2. Role of the Zn Ion in Catalysis -- 4.3. Comparison with Other Zn Hydrolases -- 4.4. Convergent Structural Evolution of Zn Hydrolases -- 4.5. Final Remark on QM/MM Studies of Enzyme Reaction Mechanisms -- 5. Conclusions -- Acknowledgments -- References -- Chapter Three: A Practical Quantum Mechanics Molecular Mechanics Method for the Dynamical Study of Reactions in Biomolecules -- 1. Introduction -- 2. Description of the Method -- 2.1. QM Method: Fireball -- 2.2. Fireball/Amber -- 3. Dynamical Analysis of Reactions in Biomolecules -- 4. Catalytic Mechanism of TIM -- 4.1. Introduction -- 4.2. Results -- 4.3. Discussion -- 5. Conclusions -- Acknowledgments -- References -- Chapter Four: Explicit Drug Re-positioning: Predicting Novel Drug-Target Interactions of the Shelved Molecules with QM/MM ... -- 1. Introduction -- 2. The Principle -- 3. Subtractive QM/MM Coupling -- 4. Additive QM/MM Coupling -- 4.1. Mechanical Embedding -- 4.1.1. Drawbacks -- 4.2. Electrostatic Embedding -- 4.3. Polarization Embedding -- 5. Ligand Polarization -- 5.1. QM-Polarized Ligand Docking -- 6. Protein Polarization -- 6.1. Boundary Treatment -- 7. QM/MM Molecular Dynamics -- 8. Geometry Optimization -- 8.1. QM/MM Exploration of Potential Energy Surfaces -- 9. Applications of QM/MM Methods to Structure-Based Drug Design -- 9.1. QM/MM Methods to Aid the Understanding of Ligand-Receptor Interactions -- 9.2. QM/MM Methods in Scoring Refinement -- 9.3. QM/MM Methods in Drug Repositioning -- 10. Five Years View Point: Future of QM/MM-Based Repositioning -- 11. Conclusion -- Acknowledgments -- References -- Links
- Chapter Five: Enzymatic Halogenases and Haloperoxidases: Computational Studies on Mechanism and Function -- 1. Introduction -- 2. Classification of Halogenases -- 2.1. Heme-Dependent Haloperoxidases -- 2.2. Vanadium-Dependent Haloperoxidases -- 2.3. Flavin Adenine Dinucleotide-Dependent Haloperoxidases -- 2.4. S-Adenosyl-l-Methionine Fluorinase -- 2.5. Nonheme Iron/α-Ketoglutarate-Dependent Halogenases -- 3. General Mechanism of α-Ketoglutarate-Dependent Halogenases -- 3.1. Generation and Characterization of the Iron(IV)-Oxo Species -- 3.2. Regioselectivity of Halogenation Versus Hydroxylation -- 3.3. Substrate Placement -- 3.4. Role of the Substrate -- 3.5. QM/MM Studies of HctB Halogenases -- 3.6. Summary -- Acknowledgments -- References -- Chapter Six: The Importance of the MM Environment and the Selection of the QM Method in QM/MM Calculations: Applications ... -- 1. Introduction -- 2. Case Studies -- 2.1. Saccharopine Reductase -- 2.2. Uroporphyrinogen Decarboxylase -- 2.3. 8R-Lipoxygenase -- 3. Conclusions -- 4. Future Directions -- Acknowledgments -- References -- Chapter Seven: QM and QM/MM Methods Compared: Case Studies on Reaction Mechanisms of Metalloenzymes -- 1. Introduction -- 2. Advantages of QM/MM -- 3. Disadvantages of QM/MM -- 4. Steric Constrains in QM Versus QM/MM Approach -- 5. Influence of the Embedding Scheme on the Reaction Chemistry: Case of EbDH -- 6. The Size of QM-Part and the Over Polarization Effect -- 7. How Can a Specific Enzymes Environment Alter the Intrinsic Nature of a Reaction? -- 8. Novel Modifications in Enzyme Structures May Produce Reactivity Patterns Only Observed Using QM/MM -- 9. Ring Hydroxylation and Rearrangement by 4-Hydroxyphenylpyruvate Dioxygenase -- 10. Conclusions -- Acknowledgments -- References
- Chapter Eight: QM/MM Studies Reveal How Substrate-Substrate and Enzyme-Substrate Interactions Modulate Retaining Glycosyl ... -- 1. Introduction -- 2. Methodological Overview -- 2.1. Model Preparation from the Crystallographic Data -- 2.2. Study of the Glycosyl Transfer Reaction -- 2.2.1. QM/MM Partition -- 2.2.2. QM/MM Methods -- 2.3. Further Analysis -- 3. Retaining GTs Mechanism -- 3.1. Neisseria meningitidis LgtC -- 3.2. Bovine α3GalT -- 3.3. Human Polypeptide-N-Acetylgalactosamine Transferase 2 -- 3.4. Implications for Retaining GTs Mechanism -- 4. Conclusions -- Acknowledgments -- References -- Chapter Nine: Excited States and Photochemistry of Chromophores in the Photoactive Proteins Explored by the Combined Quan... -- 1. Introduction -- 2. Method -- 3. Implementation of the QM/MM Approach in Protein -- 3.1. Retinal Protonated Schiff Base -- 3.2. The Photocycle of the Photoactive Yellow Protein -- 3.3. The Green Fluorescent Protein and Its S65T/H148D Double Mutant -- 4. Conclusion and Perspective -- References -- Author Index -- Subject Index -- Back Cover