Frontiers in Computational Chemistry, originally published by Bentham and now distributed by Elsevier, presents the latest research findings and methods in the diverse field of computational chemistry, focusing on molecular modeling techniques used in drug discovery and the drug development process. This includes computer-aided molecular design, drug discovery and development, lead generation, lead optimization, database management, computer and molecular graphics, and the development of new computational methods or efficient algorithms for the simulation of chemical phenomena including analyses of biological activity. In Volume 1, the leading researchers in the field have collected eight different perspectives in the application of computational methods towards drug design to provide an up-to-date rendering of the current field. This volume covers a variety of topics from G protein-coupled receptors, to the use of cheminformatics and bioinformatics, computational tools such as Molecular Mechanics Poisson-Boltzmann Surface Area, protein-protein interactions, the use of computational methods on large biological data sets, various computational methods used to identify pharmaceutically relevant targets, and more.
Author(s): Zaheer Ul-Haq, Jeffry D. Madura
Publisher: Bentham Science Publishers
Year: 2015
Language: English
Pages: 356
City: Singapore
Cover
Frontiers in Computational Chemistry (Volume 1)
Copyright
Contents
Preface
List of Contributors
1. Computational Strategies to Incorporate GPCR Complexity in Drug Design
1. INTRODUCTION
2. LIGAND-BASED APPROACHES TO EXPLORE GPCR COMPLEXITY
3. STRUCTURE-BASED METHODS FOR THE STUDY OF GPCRs
3.1. Homology Modeling
3.2. Docking: Predicting Ligand-Receptor Interaction
3.3. Taking Advantage of New Structural Information for the Discovery of New G
3.4. Advance in GPCR Virtual Screening
3.5. Successful Optimization of Lead Structures
3.6. A Dynamic View on Different Receptor Conformational States
3.7. Monitoring the Receptor Activation Process
3.8. Analyzing Ligand-GPCR Binding Paths
3.9. Studying Higher Order Receptor Complexes to Search for New GPCR Modulator
4. COMPUTATIONAL GPCR DRUG DISCOVERY: CHALLENGES AND CONCLUSIONS
AKNOWLEDGEMENTS
CONFLICT OF INTEREST
2. Knowledge-Based Drug Repurposing: A Rational Approach Towards the Identification of Novel Medical Applications of Known Drugs
INTRODUCTION
BIOINFORMATICS AND DRUG REPURPOSING
CHEMINFORMATIC-BASED DRUG REPOSITIONING
LITERATURE-BASED DRUG REPOSITIONING
NETWORK-BASED DRUG REPOSITIONING
COMPUTER AIDED DRUG REPURPOSING FOR RARE/ORPHAN AND NEGLECTED DISEASES
VALUABLE PUBLICLY AVAILABLE RESOURCES FOR IN SILICO REPOSITIONING CAMPAIGNS
CONCLUSION
AKNOWLEDGEMENTS
CONFLICT OF INTEREST
3. Tuning the Solvation Term in the MM-PBSA/GBSA Binding Affinity Predictions
1. TUNING THE PARAMETERS SPECIFIC TO MM-PBSA
1.1. The PB Solver
1.2. Acting on the Grid Resolution and on the MS
2. TUNING THE PARAMETERS SPECIFIC TO MM-GBSA
3. MM-PBSA VS MM-GBSA
4. TUNING PARAMETERS COMMON TO PB AND GB
4.1. Tuning the Internal Dielectric Constant εin
4.2. Inclusion of Explicit Solvent Molecules
4.2.1. Inclusion of Crystallographic Water Molecules
4.2.2. Inclusion of Water Molecules Identified from MD Trajectory Analysis
4.3 “Chimera” Methods
5. ACTING ON THE NON-POLAR SOLVATION TERM
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
CONFLICT OF INTEREST
REFERENCES
4. Recent Advances in the Discovery and Development of Protein-Protein Interaction Modulators by Virtual Screening
INTRODUCTION
CHALLENGES IN TARGETING PROTEIN-PROTEIN INTERFACES
WHAT IS VIRTUAL SCREENING?
Ligand-Based Virtual Screening
Structure-Based Virtual Screening
CHEMICAL LIBRARIES FOR VIRTUAL SCREENING
PRE-TREATMENT OF BIOMOLECULE AND LIGAND
VIRTUAL SCREENING BY MOLECULAR DOCKING
STRATEGIES FOR PPIM DISCOVERY
CASE STUDIES
MODULATORS OF THE TUMOR NECROSIS FACTOR ALPHA (TNF-Α) INTERACTION
MODULATORS OF PROTEIN-PROTEIN INTERACTIONS OF THE TOLL-LIKE RECEPTOR (TLR) SIGNALLING PATHWAY
MODULATORS OF STAT3 DIMER INTERACTIONS
MODULATORS OF THE IFNΑ-IFN RECEPTOR INTERACTION
FUTURE PERSEPECTIVES
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
CONFLICT OF INTEREST
REFERENCES
5. Computational Design of Biological Systems: From Systems to Synthetic Biology
SEQUENCING TO BIOINFORMATICS TO COMPUTATIONAL BIOLOGY
A BRIEF INSIGHT TO MATHEMATICAL MODELING AND SIMULATIONS [2, 3]
BIOINSPIRED SYNTHETIC DEVICES AND THEIR MODELING INSIGHTS
MEDICAL APPLICATIONS AND NEXT GENERATION THERAPEUTICS
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
CONFLICT OF INTEREST
ABBREVIATIONS
6. Considering the Medium when Studying Biologically Active Molecules: Motivation, Options and Challenges
INTRODUCTION
SOLUTE-SOLVENT INTERACTIONS AND THEIR EFFECTS
MODELS FOR THE STUDY OF SOLUTE-SOLVENT INTERACTIONS
STUDYING A BIOLOGICALLY ACTIVE MOLECULE IN SOLUTION
CHALLENGES FOR THE WAY FORWARD
CONCLUSION
ACKNOWLEDGEMENTS
CONFLICT OF INTEREST
7. A Novel Coarse-Grained Description of Protein Structure and Folding by UNRES Force Field and Discrete Nonlinear Schrodinger Equation
UNRES FORCE FIELD
APPLICATIONS OF THE KINK MODEL
COMPARISON OF THE MODELS
ENERGY CHANGES IN KINK FORMATION
CHANGES IN SIDE-CHAIN ORIENTATION IN KINK FORMATION
N SIDE-CH
AIN ORIE
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
CONFLICT OF INTEREST
REFERENCES
8. Computational Chemistry Strategies Tackling Function and Inhibition of Pharmaceutically Relevant Targets
Michele Cascella1,2,*, Matteo Dal Peraro3,4,* and Marco De Vivo5,*
1. INTRODUCTION
S IN COM
PUTATION
AL MODE
LLING
. METHOD
2.1. Wave-Function Based Methods
2.2. Density Functional Theory
2.3. Molecular Mechanics Approaches
2.4. Hybrid Quantum Mechanics / Molecular Mechanics Methods
2.5. Conformational Sampling
2.6. Coarse Grained and Multi-Scale Simulations
3. ENZYMATIC CATALYSIS
3.1. Ribonuclease H
3.2. Phosphatase Activity in Soluble Epoxide Hydrolase
3.3. One vs. Two Metal Ions for Enzymatic Phosphoryl Transfers
4. ANTIBIOTIC RESISTANCE
4.1. Antibiotic Recognition in MexB - a RND Multidrug Efflux Pump from Pseudom
4.2. Novel Antimicrobial Peptide Dendrimer Selectively Targeting Bacterial Mem
5. MD AND QM-MM METHODS FOR DRUG DESIGN: THE CASE OF THE ENZYME FAAH
TIVES
. PERSPEC
ACKNOWLEDGEMENTS
CONFLICT OF INTEREST
REFERENCES
Subject Index
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