This unit describes the process of comparative protein structure modeling using the MODELLER program. Comparative modeling predicts the three-dimensional (3-D) structure of a protein sequence (target) based on its alignment to one or more proteins of known structure (templates). The process involves four main steps: fold assignment, target-template alignment, model building, and model evaluation. MODELLER is a computer program for comparative protein structure modeling. It can perform various tasks, including fold assignment, alignment of protein sequences, multiple alignment of protein sequences and/or structures, calculation of phylogenetic trees, and de novo modeling of loops in protein structures. The unit provides a detailed description of how to calculate comparative models using MODELLER, including the steps of fold assignment, target-template alignment, model building, and model evaluation. It also discusses frequently observed errors and some applications. The unit includes an example of modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) based on a single template using MODELLER. The unit also describes how to download and install the MODELLER software. The unit provides a detailed description of the steps involved in modeling TvLDH, including the search for suitable template structures, the conversion of the sequence to PIR file format, the selection of a template, the alignment of TvLDH with the template, the model building, and the evaluation of the model. The unit also discusses the importance of an accurate alignment, the selection of templates, and the modeling by assembly of rigid bodies, modeling by segment matching or coordinate reconstruction, and modeling by satisfaction of spatial restraints. The unit concludes with a discussion of the importance of accurate alignment, the selection of templates, and the various methods used in comparative modeling.This unit describes the process of comparative protein structure modeling using the MODELLER program. Comparative modeling predicts the three-dimensional (3-D) structure of a protein sequence (target) based on its alignment to one or more proteins of known structure (templates). The process involves four main steps: fold assignment, target-template alignment, model building, and model evaluation. MODELLER is a computer program for comparative protein structure modeling. It can perform various tasks, including fold assignment, alignment of protein sequences, multiple alignment of protein sequences and/or structures, calculation of phylogenetic trees, and de novo modeling of loops in protein structures. The unit provides a detailed description of how to calculate comparative models using MODELLER, including the steps of fold assignment, target-template alignment, model building, and model evaluation. It also discusses frequently observed errors and some applications. The unit includes an example of modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) based on a single template using MODELLER. The unit also describes how to download and install the MODELLER software. The unit provides a detailed description of the steps involved in modeling TvLDH, including the search for suitable template structures, the conversion of the sequence to PIR file format, the selection of a template, the alignment of TvLDH with the template, the model building, and the evaluation of the model. The unit also discusses the importance of an accurate alignment, the selection of templates, and the modeling by assembly of rigid bodies, modeling by segment matching or coordinate reconstruction, and modeling by satisfaction of spatial restraints. The unit concludes with a discussion of the importance of accurate alignment, the selection of templates, and the various methods used in comparative modeling.