ANN based prediction of ligand binding sites outside deep cavities to facilitate drug designing

• Published in: Current research in structural biology 2024, Vol.7, p.100144-100144, Article 100144
• Main Authors: Singh, Kalpana, Malik, Yashpal Singh
• Format: Article
• Language: English
• Subjects: Animal proteins; Artificial neural network; Drug designing; Ligand binding site prediction; R-subspace; Surface roughness
• ISSN: 2665-928X; 2665-928X
• DOI: 10.1016/j.crstbi.2024.100144

The ever-changing environmental conditions and pollution are the prime reasons for the onset of several emerging and re-merging diseases. This demands the faster designing of new drugs to curb the deadly diseases in less waiting time to cure the animals and humans. Drug molecules interact with only protein surface on specific locations termed as ligand binding sites (LBS). Therefore, the knowledge of LBS is required for rational drug designing. Existing geometrical LBS prediction methods rely on search of cavities based on the fact that 83% of the LBS found in deep cavities, however, these methods usually fail where LBS localize outside deep cavities. To overcome this challenge, the present work provides an artificial neural network (ANN) based method to predict LBS outside deep cavities in animal proteins including human to facilitate drug designing. In the present work a feed-forward backpropagation neural network was trained by utilizing 38 structural, atomic, physiochemical, and evolutionary discriminant features of LBS and non-LBS residues localized in the extracted roughest patch on protein surface. The performance of this ANN based prediction method was found 76% better for those proteins where cavity subspace (extracted by MetaPocket 2.0, a consensus method) failed to predict LBS due to their localization outside the deep cavities. The prediction of LBS outside deep cavities will facilitate in drug designing for the proteins where it is not possible due to lack of LBS information as the geometrical LBS prediction methods rely on extraction of deep cavities. [Display omitted] •Most of existing methods rely on cavity search, so in ∼17% cases fail to predict LBS where it localize outside deep cavities.•Accuracy of ANN based LBS prediction method for proteins having LBS outside deep cavities is 76%.•LBS prediction outside deep cavities will facilitate in drug designing, which was not possible due to lack of LBS information.