Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions / edited by Tatyana Karabencheva-Christova.
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| Online Access: |
Full Text (via ScienceDirect) |
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| Other Authors: | |
| Format: | eBook |
| Language: | English |
| Published: |
Waltham, MA :
Academic Press,
2015.
|
| Series: | Advances in protein chemistry and structural biology ;
v. 100. |
| Subjects: |
Table of Contents:
- 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 Zones5.2. 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 Jarzynskiś 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 HyDRA2.2. 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 Coordination3.4. 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 Biomolecules1. 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.