Ramdas S Pophale | PubMed Health

PubMed2002

Developing a methodology for an inverse quantitative structure-activity relationship using the signature molecular descriptor.

The concept of signature as a molecular descriptor is introduced and various topological indices used in quantitative structure-activity relationships (QSARs) are expressed as functions of the new descriptor. The effectiveness of signature versus commonly used descriptors in QSAR analysis is demonstrated by correlating the activities of 121 HIV-1 protease inhibitors. Our approach to the inverse-QSAR problem consists of first finding the optimum sets of descriptor values best matching a target activity and then generating a focused library of candidate structures from the solution set of descriptor values. Both steps are facilitated by the use of signature.

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The signature molecular descriptor. 1. Using extended valence sequences in QSAR and QSPR studies.

We present a new descriptor named signature based on extended valence sequence. The signature of an atom is a canonical representation of the atom's environment up to a predefined height h. The signature of a molecule is a vector of occurrence numbers of atomic signatures. Two QSAR and QSPR models based on signature are compared with models obtained using popular molecular 2D descriptors taken from a commercially available software (Molconn-Z). One set contains the inhibition concentration at 50% for 121 HIV-1 protease inhibitors, while the second set contains 12865 octanol/water partitioning coefficients (Log P). For both data sets, the models created by signature performed comparable to those from the commercially available descriptors in both correlating the data and in predicting test set values not used in the parametrization. While probing signature's QSAR and QSPR performances, we demonstrates that for any given molecule of diameter D, there is a molecular signature of height h </= D+1, from which any 2D descriptor can be computed. As a consequence of this finding any QSAR or QSPR involving 2D descriptors can be replaced with a relationship involving occurrence number of atomic signatures.

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