Alignment-independent molecular descriptors

This chapter will focus on a thorough discussion of the second type of descriptors, the GRIND, as a representative example of the alignment-independent molecular descriptors that can be obtained from the MIF. 

Models based on alignment-independent molecular descriptors 69... 

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

Afzelius, L., Masimirembwa, C.M., Karlen, A., Andersson, T.B. and Zamora, I. (2002) Discriminant and quantitative PLS analysis of competitive CYP2C9 inhibitors versus non-inhibitors using alignment independent GRIND descriptors. Journal of Computer-Aided Molecular Design, 16, 443—458. 

Pastor, M., Cruciani, G., McLay, L, Pickett, S., Glementi, S. GRid-INdependent descriptors (GRIND) a novel class of alignment-independent three-dimensional molecular descriptors. /. Med. Chem. 2000, 43, 3233-3243. 

D-molecular descriptors, alignment-independent and based on molecular interaction, called GRIND have been developed. These are autocorrelation transforms that are independent of the orientation of the molecules in 3D space. The original descriptors can be extracted from the autocorrelation transform with the ALMOND program. The basic idea is to compress the information present in 3D maps into a few 2D numerical descriptors which are very simple to understand and interpret. 

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. 

Pastor M, Cruciani G, McLay I et al. (2000) Grid-independent descriptors (GRIND) A novel class of alignment-independent Three-dimensional molecular descriptors. J Med Chem 43 3233-3243... 

Alignment-independent Descriptors from Molecular Interaction Fields... 

I 6 Alignment-independent Descriptors from Molecular Interaction Fields Table 6.1 Published applications of the GRIND (at January 2005). 

The resulting variables should not depend on the position or the orientation of the molecule, thus making the molecular descriptors alignment-independent. 

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