| Abstract
| - Virtual Screening (VS) is a computational technique that allows selection and ranking of possible hits froma library of compounds. We have carried out VS on 128 selected EGFR kinase inhibitors with GOLD andLigandFit. From the experimental crystal structure of the erlotinib−EGFR complex, three key hydrogenbonds were identified as responsible for anchoring the ligand in the active site. These are of the N−H···N,Ow−H···N, and C−H···O types. Failure to include the hydrogen-bonded water molecule that forms theOw−H···N bond leads to incorrect results. Of the three interactions, the C−H···O formed by an activatedC−H group is the best conserved. On the basis of the efficacy of these hydrogen bonds, the poses wereclassified into one of three categories: close, shifted, and misoriented. In the VS context, all three interactionsneed to be modeled correctly so that correct poses and affinities are obtained, and this happens in ligandsof the close variety. Cross scoring wherein the poses from one software are input into another for scoringand consensus scoring wherein the scores from various software packages are weighted are also helpful inobtaining better agreements.
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