Correlation intensity index-index of ideality of correlation: A hyphenated target function for furtherance of MAO-B inhibitory activity assessment

Comput Biol Chem. 2023 Nov 2;108:107975. doi: 10.1016/j.compbiolchem.2023.107975. Online ahead of print.ABSTRACTMonoamine oxidases are the enzymes involved in the management of brain homeostasis through oxidative deamination of monoamines such as neurotransmitters, tyramine etc. The excessive production of monoamine oxidase-B specifically results in numerous neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Inhibitors of monoamine oxidase-B are applied in the management of these disorders. Here in this article we have developed robust hybrid descriptor based QSAR models related to 123 monoamine oxidase-B inhibitors through CORAL software by means of Monte Carlo optimization method. Three target functions were applied to prepare QSAR models and three splits were made for each target function. The most reliable, robust and better predictive QSAR models were developed with TF3 (correlation intensity index -index of ideality of correlation). Correlation intensity index showed positive effect on QSAR models. The structural features obtained from the QSAR modeling were incorporated in newly designed molecules and exhibited positive effect on their endpoint. Significant binding interactions were represented by these molecules in docking studies. Molecule B5 displayed prominent pIC50 (8.3) and binding affinity (-11.5 kcal mol-1) towards monoamine oxidase-B.PMID:37950961 | DOI:10.1016/j.compbiolchem.2023.107975
Source: Computational Biology and Chemistry - Category: Bioinformatics Authors: Source Type: research