ARKA descriptors in QSAR

In computational chemistry and cheminformatics, ARKA descriptors in QSAR are a class of molecular descriptors used in quantitative structure–activity relationship (QSAR) modeling (or related approaches such as QSPR and SQTR), a computational method for predicting the biological activity or toxicity of chemical compounds based on their molecular structure.

Molecular descriptors are numerical values that summarize information about a molecule’s structure, topology, geometry, or physicochemical properties in a form suitable for machine learning or statistical modeling. ARKA (Arithmetic Residuals in K-Groups Analysis) descriptors differ from traditional descriptors by encoding atomic-level information through recursive autoregression techniques, which aim to capture subtle structural patterns and improve predictive accuracy. They are designed to be both interpretable and well-suited to modeling nonlinear relationships in QSAR studies.

Comparisons

While QSAR is essentially a similarity-based approach, the occurrence of activity/property cliffs may greatly reduce the predictive accuracy of the developed models.^[1] The novel Arithmetic Residuals in K-groups Analysis (ARKA) approach is a supervised dimensionality reduction technique developed by the DTC Laboratory, Jadavpur University that can easily identify activity cliffs in a data set.^[2] Activity cliffs are similar in their structures but differ considerably in their activity. The basic idea of the ARKA descriptors is to group the conventional QSAR descriptors based on a predefined criterion and then assign weightage to each descriptor in each group. ARKA descriptors have also been used to develop classification-based^[3] and regression-based^[4] QSAR models with acceptable quality statistics.

The ARKA descriptors have been used for the identification of activity cliffs in QSAR studies and/or model development by multiple researchers.^{[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]}

A tutorial presentation on the ARKA descriptors is available. Recently a multi-class ARKA framework has been proposed for improved q-RASAR model generation.^[21]