Quick Guideline for Computational Drug Design

Description

Bioinformatics allows researchers to answer biological questions with advanced computational methods which involves the application of statistics and mathematical modeling. Structural bioinformatics enables the prediction and analysis of 3D structures of macromolecules while Computer Aided Drug Designing (CADD) assists scientists to design effective active molecules against diseases. However, the concepts in structural bioinformatics and CADD can be complex to understand for students and educated laymen. This quick guideline is intended as a basic manual for beginner students and instructors involved in bioinformatics and computational chemistry courses. Readers will learn the basics of structural bioinformatics, primary and secondary analysis and prediction, structural visualization, structural analysis and molecular docking. The book provides the reader an easy to read summary of the tools and techniques in structural bioinformatics as well as their limitations. In this revised edition, the authors have updated information in a number of chapters with a specific focus on the section on protein structure visualization and evaluation. Additional information on protein-ligand interaction studies has also been provided in this new edition. Therefore, the book is a useful handbook for aspiring scholars who wish to learn the basic concepts in computational analysis of biomolecules. Cover Title Copyright End User License Agreement Contents Foreword Preface CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS Dedication Introduction to Structural Bioinformatics MOTIVATION BIOINFORMATICS Bioinformatics Approaches Static Dynamic Structural Bioinformatics Software and Tools Open-source Bioinformatics Software Web Services in Bioinformatics Virtual Screening Homology Modeling Steps of Homology Modeling Accuracy Importance of Homology modeling Homology Modeling Tools UniProt KB Structure Prediction Tools Model Validation Tools Sequence Analysis Tools Model Visualization Tools Virtual Screening and Docking Recent Advancements in Computational Drug Design REFERENCES Protein Primary Sequence Analysis MOTIVATION PROTPARAM EXPASY Introduction Brief Instructions Requirements Input Sequence Submission RESULTS INTERPRETATION CONCLUSION LIMITATIONS OF PRIMARY SEQUENCE ANALYSES ProtParam Expassy REFERENCE Secondary Structure Analyses MOTIVATION SECONDARY STRUCTURE OF PROTEINS PROFUNC Brief Instructions Requirements Input Sequence Submission Accessing of Data LIMITATIONS OF SECONDARY STRUCTURE ANALYSES TOOLS ProFunc REFERENCES 3D Structure Prediction MOTIVATION STRUCTURE PREDICTION TOOLS PHYRE2 Introduction Brief Instructions Requirements Input Sequence Submission RESULTS INTERPRETATION (RESULTS SCREEN) Secondary Structure and Disorder Prediction Domain Analysis Detailed Template Information Alignment View CONCLUSION I-TASSER Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION (OUTPUT) Structure Prediction Top 10 Threading Templates Used by I-TASSER Top 5 Final Model Predicted by I-TASSER Structurally Closely Related Protein Ligand Binding Site CONCLUSION RaptorX Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION (OUTPUT) Input Sequence and Domain Partition Prediction Results Detailed Prediction Results SWISS-MODEL Introduction Brief Instructions Requirements Input Sequence Submission RESULTS INTERPRETATION (RESULTS SCREEN) Summary Templates Models CONCLUSION 3D-JIGSAW Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION CONCLUSION INTFOLD2 Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION (OUTPUT) CONCLUSION HHPRED Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION (OUTPUT) CONCLUSION M4T Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION (OUTPUT) CONCLUSION MODELLER Introduction Downloading and Installation Modeling Steps Searching for Structures Related to PSEN2 BLAST (BASIC LOCAL ALIGNMENT SEARCHING TOOL) Template PDB File Aligning PSEN2 with the Template Model Building LIMITATIONS OF STRUCTURE PREDICTION TOOLS Phyre2 I-Tasser RaptorX Swiss-model 3D-Jigsaw Intfold2 M4T Modeller REFERENCES Protein 3D Structure Assessment, Evaluation, and Validation MOTIVATION MODEL EVALUATION TOOLS ERRAT Introduction Brief Instructions Requirements Input Sequence Submission RESULTS INTERPRETATION (OUTPUT) CONCLUSION RAMPAGE Introduction Brief Instructions Requirements Input Sequence Submission RESULTS INTERPRETATION CONCLUSION ANOLEA Introduction Brief Instructions Requirements Input RESULTS INTERPRETATION CONCLUSION MOL PROBITY Introduction Brief Instructions Requirements Input RESULTS INTERPRETATION CONCLUSION VERIFY 3D Introduction Brief Instructions Requirements Input Sequence Submission RESULTS INTERPRETATION CONCLUSION PDBSUM GENERATE Introduction Brief Instructions Requirements Input Sequence Submission Accessing Data RESULTS INTERPRETATION Output Customization of Plots LIMITATIONS OF STRUCTURE EVALUATION TOOLS ERRAT Rampage Verify3D Pdbsum REFERENCES Ligand-Based Computational Molecular Docking Analysis INTRODUCTION Brief Instruction: MOE (Molecular Operating Environment) REFERENCES Protein-Ligand Interactions MOTIVATION Molecular Operating Environment (MOE) Protein-Ligand Complex 3D Structure Visualization through MOE Load and Visualize the Complex Selection Panel Protein Active Site and Rendering Active Site Rendering Ribbon Panel Atoms Panel Contacts Panel Fog and ZClip Molecular Surfaces and Maps 2D Ligand Interaction Diagram Rendering and Export Image REFERENCE Subject Index Back Cover