Presents introductory material on protein structure and function, with an evolutionary perspectiveDescribes ten of the most cogent problems in computational biologyConsiders future routes that are likely to improve our understanding of the exquisitely specific and efficient mechanisms of protein functionIncludes a suggested reading list for further research at the end of each chapter
Utilizing high speed computational methods to extrapolate to the rest of the protein universe, the knowledge accumulated on a subset of examples, protein bioinformatics seeks to accomplish what was impossible before its invention, namely the assignment of functions or functional hypotheses for all known proteins.
The Ten Most Wanted Solutions in Protein Bioinformatics considers the ten most significant problems occupying those looking to identify the biological properties and functional roles of proteins.
- Problem One considers the challenge involved with detecting the existence of an evolutionary relationship between proteins.
- Two and Three studies the detection of local similarities between protein sequences and analysis in order to determine functional assignment.
- Four, Five, and Six look at how the knowledge of the three-dimensional structures of proteins can be experimentally determined or inferred, and then exploited to understand the role of a protein.
- Seven and Eight explore how proteins interact with each other and with ligands, both physically and logically.
- Nine moves us out of the realm of observation to discuss the possibility of designing completely new proteins tailored to specific tasks.
- And lastly, Problem Ten considers ways to modify the functional properties of proteins.
After summarizing each problem, the author looks at and evaluates the current approaches being utilized, before going on to consider some potential approaches.
Table of Contents
Problem 1 Protein Sequence Alignment
Introduction to the Problem, The Evolution of Proteins (Evolution-Based Inference of Protein Function, Orthology and Paralogy, Protein Families, Similarity Matrices, Indel Penalties, Local versus Global Alignment), How Do We Align Sequences? (Global Alignment of Two Protein Sequences:, The Needleman and Wunsch Algorithm, Local Alignment of Two Protein Sequences:, The Smith and Waterman Algorithm, Multiple-Sequence Alignments, Profiles, Hidden Markov Models, Database Searching), Reliability of Present Methods and Promising Avenues, Suggested Reading
Problem 2 Predicting Protein Features from the Sequence
Introduction to the Problem, Deterministic Patterns, Stochastic Patterns, Specificity and Sensitivity of a Feature Prediction (The ROC Curve), The Prediction of Protein Domain Boundaries, Reliability of Present Methods and Promising Avenues, Suggested Reading
Problem 3 Function Prediction
Introduction to the Problem, The Definition of Biological Function, The Function Vocabulary, Protein Names, Text Mining, Transferring Functional Annotations by Similarity, Transcriptomics, Proteomics, Promising Avenues, Suggested Reading
Problem 4 Protein Structure Prediction
Introduction to the Problem, Energetic Calculations of Protein Structures (Energy Calculation, Molecular Mechanics, Potentials of Mean Force), Searching the Protein Conformational Space (Molecular Dynamics, Monte Carlo Methods, Simulated Annealing, Genetic Algorithms), Knowledge-Based Methods, Evolution-Based Methods, Fold Recognition, Fragment-Based Methods, Natively Unfolded Proteins, Promising Avenues, Suggested Reading
Problem 5 Membrane Proteins
Introduction to the Problem, The Structure of the Membrane, The Structure of Membrane Proteins, Prediction of the Structure of Membrane Proteins, Prediction of the Topography of Membrane Proteins, Prediction of the Topology of Membrane Proteins, Prediction of the Three-Dimensional Structure of, Membrane Proteins, Promising Avenues, Suggested Reading
Problem 6 Functional Site Identification
Introduction to the Problem, Structural Genomics, Structural Superposition (Root Mean Square Deviation, Structural Superposition between Two Different, Proteins, Distance Matrices), Structural Classification of Proteins, Detecting the Active Site, Moonlight Proteins, Promising Avenues, Suggested Reading ,
Problem 7 Protein-Protein Interaction
Introduction to the Problem, Protein Interactions, Sequence-Based Methods for Predicting Interactions, Experimental Methods for Detecting Protein-Protein, Interactions, Structure-Based Methods for Predicting Interactions, Representation of Protein Structures for Docking (Computational Approaches to Include Protein, Flexibility in Docking Procedures, Searching Conformational Space for Docking, Scoring Docking Solutions), The CAPRI Experiment, Promising Avenues, Suggested Reading
Problem 8 Protein-Small Molecule Interaction
Introduction to the Problem, Search Strategies and Scoring Functions, Fragment-Based and Point-Complementarity Methods, Distance Geometry-Based Methods, Virtual Screening, The Properties of a Drug, Promising Avenues, Suggested Reading
Problem 9 Protein Design
Introduction to the Problem, Intuitive Design, Lattice Models and Automatic Methods, Promising Avenues, Suggested Reading
Problem 10 Protein Engineering
Introduction to the Problem, Combining Functions, Global Properties, Active and Binding Sites, Catalytic Antibodies, Combinatorial Design, Dissecting the Folding Pathway of Proteins, Promising Avenues, Suggested Reading
"The book is comprehensive and succinct; people on busy schedules can read it in a short period of time. ...I believe that it is a great book. I will definitely include it as a recommended text for one of my Bioinformatics Graduate courses. I highly recommend this text to anyone interested in protein bioinformatics."
-Kay C Wiese, Biomedical Engineering OnLine
"It succeeds in providing an introduction … [for] someone with little or no knowledge of protein bioinformatics. For such a reader it would provide a fairly comprehensive, but necessarily brief overview of the research challenges the field faces. … I would recommend this book to a new prospective researcher…"
-D.R.Westhead, UK Nonlinear News
"…Clarity and conciseness is apparent throughout the text, and at no point does it get weighted down by excessive detail. The text is equally adroit in its description of biological processes and structures. These are detailed in such a manner as to be easily understood by those with only a limited understanding of protein biology, without oversimplification … [This book] has something to offer both biologists and informaticians alike, treating computation techniques and biological processes in balanced amounts. If a general high-level and broad ranging discussion of the state of research in protein bioinformatics is sought, then this book comes recommended."
-Dr. Matthew J. Sullivan, Proteomics
"To introduce newcomers to this area is not an easy task and this book is a serious attempt to help many of them."
-Short Book Reviews of the ISI