Figure 1

ConTemplate methodology, demonstrated using the known structure of the EGFR kinase domain in its inactive conformation as a query and reproducing its active conformation; the RMSD between the active and inactive conformations is 4.17Å. Step 1: Selecting proteins with structural similarity to the query; only one is shown here. Step 2: Finding alternative conformations of the proteins detected in Step 1. The black arrows mark the regions with the main differences between the conformations. Step 3: Modeling putative new conformations of the query using the conformations detected in step 2 as templates; only one is shown here. The black arrows indicate the similarities between the model, template and actual known conformation in the main regions of the conformational changes.