A Basic Protein Comparative Three-Dimensional Modeling Methodological Workflow Theory and Practice

When working with proteins and studying its properties, it is crucial to have access to the three-dimensional structure of the molecule. If experimentally solved structures are not available, comparative modeling techniques can be used to generate useful protein models to subsidize structure-based research projects. In recent years, with Bioinformatics becoming the basis for the study of protein structures, there is a crescent need for the exposure of details about the algorithms behind the softwares and servers, as well as a need for protocols to guide in silico predictive experiments. In this article, we explore different steps of the comparative modeling technique, such as template identification, sequence alignment, generation of candidate structures and quality assessment, its peculiarities and theoretical description. We then present a practical step-by-step workflow, to support the Biologist on the in silico generation of protein structures. Finally, we explore further steps on comparative modeling, presenting perspectives to the study of protein structures through Bioinformatics. We trust that this is a thorough guide for beginners that wish to work on the comparative modeling of proteins.