Prediction, validation, and analysis of protein structures: A beginner’s guide

Determining the three-dimensional structure of a protein is required for studying its interactions, dynamics, structure-function relationship, and even inhibitor designing. Though protein structures have become essential for contemporary research, the gap between the available number of protein sequences and known protein structures is increasing exponentially. Apart from in vitro structural determination methods like NMR spectroscopy, X-ray crystallography, and cryo-electron microscopy, several in silico methods are now available for predicting the structure of proteins. These methods have advanced by leaps and bounds in the past few decades owing to their potential applications in the field of biotechnology and medicine. Moreover, it is not the prediction but the validation and analysis of these predicted structures that form the core of protein modeling. This chapter explains how a protein structure can be modeled from scratch using in silico tools and further identify the best model through validation and refinement. Also, we highlight the technological advancements enabled by recent breakthroughs in this field. These tools, if used precisely, can provide valuable information in protein structure studies.