A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling

Lactate dehydrogenase (LDH) is a tetramer enzyme that converts pyruvate to lactate reversibly. This enzyme becomes important because it is associated with diseases such as cancers, heart disease, liver problems, and most importantly, corona disease. As a system-based method, proteochemometrics does not require knowledge of the protein's three-dimensional structure, but rather depends on the amino acid sequence and protein descriptors. Here, we applied this methodology to model a set of LDHA and LDHB isoenzyme inhibitors. To implement the proteochemetrics method, the camb package in the R Studio Server programming environment was used. The activity of 312 compounds of LDHA and LDHB isoenzyme inhibitors from the valid Binding DB database was retrieved. The proteochemometrics method was applied to three machine learning algorithms gradient amplification model, random forest, and support vector machine as regression methods to find the best model. Through the combination of different models into an ensemble (greedy and stacking optimization), we explored the possibility of improving the performance of models. For the RF best ensemble model of inhibitors of LDHA and LDHB isoenzymes, and were 0.66 and 0.62, respectively. LDH inhibitory activation is influenced by Morgan fingerprints and topological structure descriptors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13065-023-00991-6.