The 3D structure of protein is an important basis for understanding its biological function and structure-based drug design. With the rapid development of structural biology, the measurement speed of protein 3D structure by NMR or X-ray crystallography has been greatly improved. However, the 3D structure of some proteins which molecular weight are too large or difficult to crystallize, still difficult to determine. In this case, the 3D structure of protein must be constructed by means of computational simulation. Among numberous computer modeling methods, homology modeling is the most mature technology, with the highest accuracy and the most reliable result. The basic assumption of homology modeling is that if unknown structural protein A and known structural protein B have homology in sequence, structure and function, protein A can use protein B as a template to construct its full atomic 3D structure.
The process of constructing a homologous model is usually concise and clear. Firstly, use the sequence similarity search tool to search for known structural proteins with high sequence similarity for the query sequence as a candidate template. Secondly, align the query sequence with the candidate template, and use the sequence identity as an indicator to select one or more template proteins as the final template. After alignment, all the atomic coordinates of those residues that are exactly the same as the template sequence are completely copied from the template, while those similar residues only have backbone atoms taken from the template and the side chain coordinates are constructed separately, and those missing sequences are filled by searching a loop database. Finally, the prediction model is optimized under specific potential field parameters to obtain the final model.
Wecomput provides high-quality homology modeling services. The results can help researchers understand the structural properties of the target protein and analyze its “structure-function” relationship. The model can be used for drug screening, discovery of potential therapeutic drugs for certain diseases, or research the interaction mode of the target and the drug, etc.