Figure 1

Generating a sample of conformations for a protein surface patch. We illustrate our method on the complex between the human MHC class I glycoprotein HLA-A2 and the T-cell co-receptor CD8, whose structure is available in the PDB [37] under the acronym 1AKJ: the interface is the opaque region where the receptor (HLA-A2: blue) and ligand (CD8: green) come into close contact. 1) The receptor is divided into patches; we select one that contains nine residues. 2) To allow for side chain flexibility, we generate different side chain conformations for each of the nine residues in the selected patch; as an illustration, we show 6 rotamers of a tryptophan (top), 3 rotamers of an aspartic acid, and 28 rotamers of a glutamine (purple). This results in 1,741,824 possible conformations for the patch. 3) These conformations are filtered according to an energy function using a self consistent mean field approach, 4) then clustered by k-means, reducing the number of docking candidates to 50.