inSARa: intuitive and interactive SAR interpretation by reduced graphs and hierarchical MCS-based network navigation.
The analysis of Structure-Activity-Relationships (SAR) of small molecules is a fundamental task in drug discovery. Although a large number of methods are already published, there is still a strong need for novel intuitive approaches. The inSARa (intuitive networks for Structure-Activity Relationships analysis) method introduced herein takes advantage of the synergistic combination of reduced graphs (RG) and the intuitive maximum common substructure (MCS) concept. The main feature of the inSARa concept is a hierarchical network structure of clearly defined substructure relationships based on common pharmacophoric features. Thus, straightforward SAR interpretation is possible by interactive network navigation. When focusing on a set of active molecules at one single target, the resulting inSARa networks are shown to be valuable for various essential tasks in SAR analysis, such as the identification of activity cliffs or "activity switches", bioisosteric exchanges, common pharmacophoric features, or "SAR hotspots".
Institute of Medicinal and Pharmaceutical Chemistry, University of Technology Braunschweig , Beethovenstrasse 55, 38106 Braunschweig, Germany.
Sabrina
S
Wollenhaupt
Knut
K
Baumann
D003196:Computer Graphics; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations