Thormann, Michael and Klamt, Andreas and Wichmann, Karin (2012) COSMOsim3D: 3D-Similarity and Alignment Based on COSMO Polarization Charge Densities. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 52 (8). pp. 2149-2156. ISSN 1549-9596,
Full text not available from this repository. (Request a copy)Abstract
COSMO sigma-surfaces resulting from quantum chemical calculations of molecules in a simulated conductor, and their histograms, the so-called sigma-profiles, are widely proven to provide a very suitable and almost complete basis for the description of molecular interactions in condensed systems. The COSMOsim method therefore introduced a global measure of molecular similarity on the basis of similarity of sigma-profiles, but it had the disadvantage of neglecting the 3D distribution of molecular polarities, which is crucially determining all ligand receptor binding. This disadvantage is now overcome by COSMOsim3D, which is a logical and physically sound extension of the COSMOsim method, which uses local sigma-profiles on a spatial grid. This new method is used to measure intermolecular similarities on the basis of the 3D representation of the surface polarization charge densities a of the target and the probe molecule. The probe molecule is translated and rotated in space in order to maximize the sum of local sigma-profile similarities between target and probe. This sum, the COSMOsim3D similarity, is a powerful descriptor of ligand similarity and allows for a good discrimination between bioisosters and random pairs. Validation experiments using about 600 pharmacological activity classes in the MDDR database are given. Furthermore, COSMOsim3D represents a unique and very robust method for a field based ligand ligand alignment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RS; PREDICTION; SOLVATION; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2020 06:29 |
| Last Modified: | 07 May 2020 06:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18322 |
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