|Computational Biophysics||Structural Bioinformatics|
The most popular method for obtaining 3D structures from sequence is comparative modeling. It is based on the observation that structures are more conserved than sequences. Once a homologous sequence with a 3D structure is identified, it is possible to use it to build the 3D structure of the sequence of interest. Its efficiency strongly depends on the sequence similarity between the target and the templates. The main limitation lies in the identification of a relevant structural template. The second limitation concerns the quality of the alignment. For membrane proteins, the number of templates is extremely small, which limits the application of homology modeling. Moreover, membrane proteins are constrained by the membrane environment (mainly 2D), which limits the diversity of the proteins folds compared to soluble proteins. Hence, de novo or ab initio prediction can be envisaged. The team will contribute to both aspects and the main steps are summarized below.