Introduction to Protein Structure Prediction

TL;DR

This chapter introduces the challenges and methods of protein 3D structure prediction from a single sequence, discussing template-based and free modeling, validation, and the sustainability of the single-fold concept.

Contribution

It provides an overview of current modeling techniques, validation practices, and critically examines the feasibility of accurate predictions and the single-fold hypothesis.

Findings

Prediction remains unsolved for quantitative accuracy.

Template-based modeling can generate high-accuracy structures when templates are available.

Structural validation methods are essential for assessing prediction reliability.

Abstract

This chapter gives a graceful introduction to problem of protein three- dimensional structure prediction, and focuses on how to make structural sense out of a single input sequence with unknown structure, the 'query' or 'target' sequence. We give an overview of the different classes of modelling techniques, notably template-based and template free. We also discuss the way in which structural predictions are validated within the global com- munity, and elaborate on the extent to which predicted structures may be trusted and used in practice. Finally we discuss whether the concept of a sin- gle fold pertaining to a protein structure is sustainable given recent insights. In short, we conclude that the general protein three-dimensional structure prediction problem remains unsolved, especially if we desire quantitative predictions. However, if a homologous structural template is available in the PDB model or reasonable to high accuracy may be generated.