Alignment independent QSAR

Caroli, A., Botta, G., Brosch, G., Massa, S. and Mai, A. (2008) Class 11-selective histone deacetylase inhibitors. Part 2 alignment-independent GRIND 3-D QSAR, homology and docking studies. European Journal of Medicinal Chemistry, 43, 621-632. 

Key Words 2D-QSAR traditional QSAR 3D-QSAR nD-QSAR 4D-QSAR receptor-independent QSAR receptor-dependent QSAR high throughput screening alignment conformation chemometrics principal components analysis partial least squares artificial neural networks support vector machines Binary-QSAR selecting QSAR descriptors. 

The major hurdle to overcome in the development of 3D-QSAR models using steric, electrostatic, or lipophilic fields is related to both conformation selection and subsequent suitable overlay (alignment) of compounds. Therefore, it is of some interest to provide a conformation-ally sensitive lipophilicity descriptor that is alignment-independent. In this chapter we describe the derivation and parametrization of a new descriptor called 3D-LogP and demonstrate both its conformational sensitivity and its effectiveness in QSAR analysis. The 3D-LogP descriptor provides such a representation in the form of a rapidly computable description of the local lipophilicity at points on a user-defined molecular surface. 

Key Words 3D-QSAR hydrophobicity lipophilicity 3D-LogP conformation-dependent lipophilicity alignment-independent 3D descriptor molecular lipophilicity potential (MLP) ADME-related descriptor. 

All QSAR analysis was carried out using the program ALMOND 3.2.0 and grid alignment independent descriptors (GRIND). 

Baumann, K. (2002a) An alignment-independent versatile structure descriptor for QSAR and QSPR based on the distribution of molecular features. 

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