Protein Ligand Complex Guided Approach for Virtual Screening

• Published in: Combinatorial chemistry & high throughput screening Vol. 18; no. 6; p. 577
• Main Authors: Karthikeyan, Muthukumarasamy, Pandit, Deepak, Vyas, Renu
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2015
• Subjects: Amino Acid Sequence; Computer Simulation; Datasets as Topic; Drug Design; Ligands; Models, Molecular; Proteins - chemistry; Small Molecule Libraries - chemical synthesis; Small Molecule Libraries - chemistry
• ISSN: 1875-5402
• DOI: 10.2174/1386207318666150703112620

The target ligand association data is a rich source of information which is not exploited enough for drug design efforts in virtual screening. A java based open-source toolkit for Protein Ligand Network Extraction (J-ProLiNE) focused on protein-ligand complex analysis with several features integrated in a distributed computing network has been developed. Sequence alignment and similarity search components have been automated to yield local, global alignment scores along with similarity and distance scores. 10000 proteins with co-crystallized ligands from pdb and MOAD databases were extracted and analyzed for revealing relationships between targets, ligands and scaffolds. Through this analysis, we could generate a protein ligand network to identify the promiscuous and selective scaffolds for multiple classes of proteins targets. Using J-ProLiNE we created a 507 x 507 matrix of protein targets and native ligands belonging to six enzyme classes and analyzed the results to elucidate the protein-protein, protein-ligand and ligand-ligand interactions. In yet another application of the J-ProLiNE software, we were able to process kinase related information stored in US patents to construct disease-gene-ligand-scaffold networks. It is hoped that the studies presented here will enable target ligand knowledge based virtual screening for inhibitor design.