Protein Structure Prediction Concepts and Applications

by Tramontano, Anna; Lesk, Arthur M.

• ISBN13: 9783527311675
• ISBN10: 352731167X
• Edition: 1st
• Format: Paperback
• Copyright: 2006-02-20
• Publisher: Wiley-VCH

Summary

While most textbooks on bioinformatics focus on genetic algorithms and treat protein structure prediction only superficially, this course book assumes a novel and unique focus. Adopting a didactic approach, the author explains all the current methods in terms of their reliability, limitations and user-friendliness. She provides practical examples to help first-time users become familiar with the possibilities and pitfalls of computer-based structure prediction, making this a must-have for students and researchers.

Author Biography

Anna Tramontano is Professor of Biochemistry at the Medical Faculty of the University of Rome "La Sapienza" since 2001. She received her PhD in Physics from the University of Naples (Italy) in 1980 and held various appointments at research institutes in Europe and in the U.S. before becoming Professor of Bioinformatics at the University of Milan in 1990. From 1996 to 2001 she held the position as director of Computational Biology and Chemistry at the Merck Research Laboratories in Rome.
Anna Tramontano is among the organizers of the CASP (critical assessment of protein structure prediction) conferences and is on the editorial boards of several journals.

Table of Contents

SEQUENCE, FUNCTION, AND STRUCTURE RELATIONSHIPS

Protein Structure

The Properties of Amino Acids

Experimental Determination of Protein Structures

The PDB Protein Structure Data Archive

Classification of Protein Structures

The Protein-folding Problem

Inference of Function from Structure

The Evolution of Protein Function

The Evolution of Protein Structure

Relationship Between Evolution of Sequence and Evolution of Structure

RELIABILITY OF METHODS FOR PREDICTION OF PROTEIN STRUCTURE

Prediction of Secondary Structure

Prediction of Tertiary Structure

Benchmarking a Method of Prediction

Blind Automatic Assessments

The CASP Experiments

AB-INITIO METHODS FOR PREDICTION OF PROTEIN STRUCTURES

The Energy of a Protein Configuration

Interactions and Energies

Covalent Interactions

Electrostatic Interactions

Potential-energy Functions

Statistical-mechanics Potentials

Energy Minimization

Molecular Dynamics

Other Search Methods: Monte Carlo and Genetic Algorithms

Effectiveness of Ab-initio Methods for Folding a Protein

EVOLUTIONARY-BASED METHODS FOR PREDICTING PROTEIN STRUCTURE: COMPARATIVE MODELING

Theoretical Basis of Comparative Modeling

Detection of Evolutionary Relationships from Sequences

The Needleman and Wunsch Algorithm

Substitution Matrices

Template(s) Identification Part I

The Problem of Domains

Alignment

Template(s) Identification Part II

Building the Main Chain of the Core

Building Structurally Divergent Regions

A Special Case: Immunoglobulins

Side-chains

Model Optimization and Other Approaches

Effectiveness of Comparative Modeling Methods

SEQUENCE?STRUCTURE FITNESS IDENTIFICATION: FOLD-RECOGNITION METHODS

The Theoretical Basis of Fold-recognition

Profile-based Methods for Fold-recognition

Threading Methods

Profile?Profile Methods

Construction and Optimization of the Model

METHODS USED TO PREDICT NEW FOLDS: FRAGMENT-BASED METHODS

Fragment-based Methods

Splitting the Sequence into Fragments and Selecting Fragments from the Database

Generation of Structures

LOW-DIMENSIONALITY PREDICTION: SECONDARY STRUCTURE AND CONTACT PREDICTION

A Short History of Secondary-structure Prediction Methods

Automatic-learning Methods

Secondary-structure Prediction Methods Based on Automatic Learning Techniques

Prediction of Long-range Contacts

MEMBRANE PROTEINS

Prediction of the Secondary Structure of Membrane Proteins

The Hydrophobic Moment

Prediction of the Topology of Membrane Proteins

APPLICATIONS AND EXAMPLES

Early Attempts

The HIV Protease

Leptin and Obesity

The Envelope Glycoprotein of the Hepatitis C Virus

HCV Protease

Cyclic Nucleotide Gated Channels

The Effectiveness of Models of Proteins in Drug Discovery

The Effectiveness of Models of Proteins in X-ray Structure Solution