This unit, authored by Benjamin Webb and Andrej Sali from the University of California at San Francisco, provides a comprehensive guide to using the program MODELLER for comparative protein structure modeling. Comparative modeling is a powerful technique for predicting the 3-D structure of a protein sequence based on its alignment to one or more known protein structures. The process involves four main steps: fold assignment, target-template alignment, model building, and model evaluation. The unit covers each step in detail, including common errors and applications, with a focus on the modeling of lactate dehydrogenase from *Trichomonas vaginalis* (TvLDH) as an example. It also provides instructions for downloading and installing MODELLER, a software tool that automates the comparative modeling process. The unit emphasizes the importance of accurate alignments and discusses various methods for selecting suitable templates, aligning sequences with templates, and building and evaluating models. Additionally, it highlights the role of MODELLER in handling complex cases and incorporating additional information to improve model accuracy.This unit, authored by Benjamin Webb and Andrej Sali from the University of California at San Francisco, provides a comprehensive guide to using the program MODELLER for comparative protein structure modeling. Comparative modeling is a powerful technique for predicting the 3-D structure of a protein sequence based on its alignment to one or more known protein structures. The process involves four main steps: fold assignment, target-template alignment, model building, and model evaluation. The unit covers each step in detail, including common errors and applications, with a focus on the modeling of lactate dehydrogenase from *Trichomonas vaginalis* (TvLDH) as an example. It also provides instructions for downloading and installing MODELLER, a software tool that automates the comparative modeling process. The unit emphasizes the importance of accurate alignments and discusses various methods for selecting suitable templates, aligning sequences with templates, and building and evaluating models. Additionally, it highlights the role of MODELLER in handling complex cases and incorporating additional information to improve model accuracy.