|As part of the ATP-binding cassette transporter superfamily ABCB1 (P-gp) exports a multitude of xenobiotics and is strongly connected to multi-drug resistance (MDR). A valid crystal structure of this protein is still missing and ligand based approaches are the methods of choice. Its high promiscuity and implications in drug/drug interactions and brain permeation of drugs renders prediction of possible substrates highly demanding. Recently we could demonstrate that Similarity Based Descriptors (SIBAR) are a useful tool to establish predictive in silico models for drug/ABCB1 interaction. Based on a reference set representing satellite structures in the chemical space we compared a 3D-shape based comparison (ROCS) with SIBAR based on VSA and Volsurf descriptors. Our results validated on an external test set showed an overall prediction accuracy of 74 % with the VolSurf Descriptors achieving the best overall classification performance. |
Financial support provided by the Austrian Science fund (L344-N17 and F3502).
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster