A Virtual Active Compound Produced from the Negative Image of a Ligand-binding Pocket, and its Application to in-silico Drug Screening
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We developed a new structure-based in-silico screening method using a negative image of a ligand-binding pocket and a multi-protein–compound interaction matrix. Based on the structure of the ligand pocket of the target protein, we designed a negative image, which consists of virtual atoms whose radii are close to those of carbon atoms. The virtual atoms fit the pocket ideally and achieve an optimal Coulomb interaction. A protein–compound docking program calculates the protein–compound interaction matrix for many proteins and many compounds including the negative image, which can be treated as a virtual compound. With specific attention to a vector of docking scores for a single compound with many proteins, we selected a compound whose score vector was similar to that of the negative image as a candidate hit compound. This method was applied to representative target proteins and showed high database enrichment with a relatively quick procedure.
KeywordsDatabase enrichment Docking score Flexible docking Negative image Receptor–ligand docking Virtual atom Virtual compound Virtual screening
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This work was supported by grants from the New Energy and Industrial Technology Development Organization of Japan (NEDO) and the Ministry of Economy, Trade, and Industry (METI) of Japan.
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