Combined quantum mechanical and molecular mechanical modelling of biomolecular interactions / Tatyana Karabencheva-Christova.

Format:

Book

Author/Creator:

Karabencheva-Christova, Tatyana, author.

Series:

Advances in protein chemistry and structural biology ; Volume 100.

Advances in protein chemistry and structural biology, 1876-1623 ; Volume 100

Language:

English

Subjects (All):

Quantum chemistry.

Biomolecules--Analysis.

Biomolecules.

Physical Description:

1 online resource (0 p.)

Edition:

First edition.

Place of Publication:

Amsterdam, [Netherlands] : Academic Press, 2015.

Language Note:

English

Summary:

" Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions" continues the tradition of the "Advances" "in Protein Chemistry and Structural Biology" series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics. Describes advances in application of powerful techniques in the biosciencesProvides cutting-edge developments in protein chemistry and structural biologyChapters are written by authorities in their field Targeted to a wide audience of researchers, specialists, and students

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 Zones

5.2. Treatment of Long-Range Electrostatic Interactions

6. Conclusions

References

Chapter Two: Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorit...

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

Chapter Three: A Practical Quantum Mechanics Molecular Mechanics Method for the Dynamical Study of Reactions in Biomolecules

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

Chapter Four: Explicit Drug Re-positioning: Predicting Novel Drug-Target Interactions of the Shelved Molecules with QM/MM ...

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

Links.

Chapter Five: Enzymatic Halogenases and Haloperoxidases: Computational Studies on Mechanism and Function

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

Chapter Six: The Importance of the MM Environment and the Selection of the QM Method in QM/MM Calculations: Applications ...

2. Case Studies

2.1. Saccharopine Reductase

2.2. Uroporphyrinogen Decarboxylase

2.3. 8R-Lipoxygenase

3. Conclusions

4. Future Directions

Chapter Seven: QM and QM/MM Methods Compared: Case Studies on Reaction Mechanisms of Metalloenzymes

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

References.

Chapter Eight: QM/MM Studies Reveal How Substrate-Substrate and Enzyme-Substrate Interactions Modulate Retaining Glycosyl ...

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

Chapter Nine: Excited States and Photochemistry of Chromophores in the Photoactive Proteins Explored by the Combined Quan...

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

Author Index

Subject Index

Back Cover.

Notes:

Description based upon print version of record.

Includes bibliographical references at the end of each chapters and indexes.

Description based on online resource; title from PDF title page (ebrary, viewed December 04, 2015).

ISBN:

9780128020180

0128020180

9780128020036

0128020032

OCLC:

932329900