CoSSDb: A Database of Co-crystallized Ligand Sub-structures for Anticancer Lead Designing & Optimization

Abstract

The Discovery of the novel optimized structures of small molecules for selective targeting is one of the challenging tasks in drug designing. Bioisosteres are the key components of the lead compound, which provide hidden power to the compound scaffold for selective targeting. We are presenting a database, named CoSSDb which stands for Co-crystallized Sub-Structure Database. The CoSSDb contains ligand sub-structures as possible bioisosteres. extracted from PDB files, available in Protein Data Bank. Sub-structures were extracted through an algorithm, which utilizes the location of atoms in the 3D domain of the complex ligand & protein. It processes the relative positioning of atoms for demarcation of the influential part of the ligand, which interacts with macromolecule and provides potency to that ligand for binding with a specific binding pocket of the protein. The algorithm was used to extract sub-structures from the ligands co-crystallized with proteins involved in cancer. About 7721 x-ray crystallography PDB files were processed, and 654 non-redundant substructures were identified. These sub-structures will be useful during designing & optimization of novel ligands for selective targets. The database is freely accessible at ‘https://opticket49.wixsite.com/substructdb’.