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We propose the novel approach of '<jats:italic>in silico<\/jats:italic> panning' which consists of a two-stage screening, involving affinity selection by docking simulation and evolution of the peptide ligand using genetic algorithms (GAs). <jats:italic>In silico<\/jats:italic> panning was successfully applied to the selection of peptide inhibitor for water-soluble quinoprotein glucose dehydrogenase (PQQGDH).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The evolution of peptide ligands for a target enzyme was achieved by combining a docking simulation with evolution of the peptide ligand using genetic algorithms (GAs), which mimic Darwinian evolution. Designation of the target area as next to the substrate-binding site of the enzyme in the docking simulation enabled the selection of a non-competitive inhibitor. In all, four rounds of selection were carried out on the computer; the distribution of the docking energy decreased gradually for each generation and improvements in the docking energy were observed over the four rounds of selection. One of the top three selected peptides with the lowest docking energy, 'SERG' showed an inhibitory effect with <jats:italic>K<\/jats:italic>\n              <jats:sub>i<\/jats:sub> value of 20 \u03bcM. PQQGDH activity, in terms of the <jats:italic>V<\/jats:italic>\n              <jats:sub>max<\/jats:sub> value, was 3-fold lower than that of the wild-type enzyme in the presence of this peptide. The mechanism of the SERG blockage of the enzyme was identified as non-competitive inhibition. We confirmed the specific binding of the peptide, and its equilibrium dissociation constant (<jats:italic>K<\/jats:italic>\n              <jats:sub>D<\/jats:sub>) value was calculated as 60 \u03bcM by surface plasmon resonance (SPR) analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We demonstrate an effective methodology of <jats:italic>in silico<\/jats:italic> panning for the selection of a non-competitive peptide inhibitor from small virtual peptide library. This study is the first to demonstrate the usefulness of <jats:italic>in silico<\/jats:italic> evolution using experimental data. Our study highlights the usefulness of this strategy for structure-based screening of enzyme inhibitors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-8-11","type":"journal-article","created":{"date-parts":[[2007,1,12]],"date-time":"2007-01-12T19:14:55Z","timestamp":1168629295000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["In silico panning for a non-competitive peptide inhibitor"],"prefix":"10.1186","volume":"8","author":[{"given":"Yukiko","family":"Yagi","sequence":"first","affiliation":[]},{"given":"Kotaro","family":"Terada","sequence":"additional","affiliation":[]},{"given":"Takahisa","family":"Noma","sequence":"additional","affiliation":[]},{"given":"Kazunori","family":"Ikebukuro","sequence":"additional","affiliation":[]},{"given":"Koji","family":"Sode","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2007,1,12]]},"reference":[{"key":"1383_CR1","first-page":"17","volume":"83","author":"M V","year":"2005","unstructured":"V M: WATCHING PEPTIDE DRUGS GROW UP. 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