Structural Insights into EGFR-Erlotinib Complex

The crystal structure of EGFR complexed with erlotinib (PDB ID: 1M17) [39 (link)] was downloaded from Protein Data Bank (PDB). The 3D structure of the drug (erlotinib) was obtained from the ZINC database, whilst the 3D structures of vinyl sulfone derivatives were generated using the Gaussian 09 program. Note that the vinyl sulfone derivatives were constructed according to their availability from previous study [21 (link),22 (link),23 (link),24 (link)]. All the ligands were optimized using the Gaussian 09 program (HF/6–31d) as per the standard protocol [42 (link),43 (link),44 ]. The protonation state of all studied ligands was characterized using the ChemAxon [45 (link)].
For system validation, the crystalized ligands were defined as a center in the active site for redocking using CDOCKER programs and the results are shown in Supplementary Figure S1. The docking protocols of EGFR system was set as 15 Å for sphere docking and docked into the binding pocket with 100 independent runs. The binding between protein and compounds/drug was visualized using the Accelrys Discovery Studio 3.0 (Accelrys Inc., Cambridge, UK) and UCSF Chimera package [46 (link)].