Homologous modeling is a general term for converting primary sequences into 3D structures based on template proteins. Homology modeling refers to the construction of an atomic resolution model of the "target" protein from its "amino acid" sequence and the experimental three-dimensional structure ("template") of the related homologous protein. Homology modeling relies on the identification of one or more known protein structures that may be similar to the structure of the query sequence, and by generating an alignment that maps residues in the query sequence to residues in the template sequence, it has been proven the protein structure is more conserved in homologues than the protein sequence, but sequences with less than 20% sequence identity may have very different structures. Here we introduce the tutorial of swiss model for modeling.

Tutorial

First, enter swiss-model, enter the sequence, and click "Search For Templates" to simply search for the template. After the search is completed, you can choose a template for modeling according to your needs. Click "Build Model" to search for templates and automatically select the template for modeling. Below, use "Build Model" for automatic modeling.

The figure below is the modeling interface. It can be seen that a total of 50 Template templates were searched out, and then a total of 5 Models were built. Here you can choose a model that looks beautiful.

Download the model as PDB format and put it into VMD visualization, the whole protein gives a complex and delicate feeling.

Predictive effect

• If the target sequence is extremely similar to the template sequence, then the homology modeling method is the most accurate method.
• If the degree of agreement can reach 30%, the accuracy of the model can reach 80%, and the model can be used to find functional sites and infer functional relationships.
• If the degree of agreement can reach 50%, the accuracy of the model can reach 95%, and a site-specific mutation experiment can be designed according to the model, and the crystal structure rotation can be designed to assist in the determination of the true structure.
• If the degree of agreement can reach more than 70%, we can think that the prediction model completely represents the real result, and can be used for molecular screening, molecular docking, and structural and functional studies of drug design.

Results evaluation

• GMQE

GMQE (Global Model Quality Estimation) is a quality estimation that combines the attributes of target-template alignment and template search methods. The resulting GMQE score is expressed as a number between 0 and 1, reflecting the expected accuracy of the model built using this alignment and template and the coverage of the target. The higher the number, the higher the reliability.

• QMEAN

The scores of this model are comparable to those expected from experimental structures of similar size. The QMEAN score near the value of 0 indicates that the model structure has a good agreement with the experimental structure of similar size. A score of -4.0 or below indicates that the quality of the model is low.