Comparative Protein Structure Modeling Using MODELLER

This protocol describes comparative (homology) protein structure modeling, which predicts a target protein's three-dimensional structure primarily from its alignment to one or more homologous proteins whose structures are already known. It walks through the four steps of the process, fold assignment, target-template alignment, model building, and model evaluation, and shows how to carry them out with the MODELLER program, including how to download and install the software.

Beyond the mechanics, the unit explains how to use the ModBase database of precomputed comparative models, discusses frequently observed errors and some applications of the method, and grounds the instructions in a concrete worked example: modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH). By combining the full modeling pipeline with a database resource and a step-by-step example, it serves as a hands-on reference for producing comparative protein models.