edoc

Searching for bioactive conformations of drug-like ligands with current force fields: how good are we?

Gürsoy, Oya and Smieško, Martin. (2017) Searching for bioactive conformations of drug-like ligands with current force fields: how good are we? Journal of Cheminformatics, 9 (29). pp. 1-13.

[img]
Preview
PDF - Published Version
Available under License CC BY (Attribution).

2138Kb

Official URL: http://edoc.unibas.ch/55315/

Downloads: Statistics Overview

Abstract

Drug-like ligands obtained from protein–ligand complexes deposited in the Protein Databank were subjected to conformational searching using various force fields and solvation settings. For each ligand, the resulting conformer pool was examined for the presence of the bioactive (crystal pose-like) conformation. Similarity of conformers toward the crystal-pose was quantified as the best achievable root mean squared deviation (RMSD, heavy atoms only). Analyzing the conformer pools generated by various force fields revealed only small differences in the likelihood of finding a crystal pose-like conformation. However, employing different solvents in the conformational search was found to be very important for achieving RMSDs below 1.0 Å. The best statistical values of likelihood were observed with a recently released force field covering a large portion of dihedral angles occurring in drug-like compounds in combination with the water as solvent. In order to enable computational chemists and modelers to efficiently use available software tools, we have additionally performed several focused analyses on ligands, grouped according to descriptors most relevant for the rational drug design.
Faculties and Departments:05 Faculty of Science
05 Faculty of Science > Departement Pharmazeutische Wissenschaften
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Ehemalige Einheiten Pharmazie > Molecular Modeling (Vedani)
UniBasel Contributors:Smiesko, Martin and Gürsoy, Oya
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
e-ISSN:1758-2946
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:28 Nov 2017 13:03
Deposited On:16 Oct 2017 09:10

Repository Staff Only: item control page