Exploring the role of water molecules for docking and receptor guided 3D-QSAR analysis of naphthyridine derivatives as spleen tyrosine kinase (Syk) inhibitors.
In the present study, 3D-QSAR analysis was performed utilizing docking based alignment of [1,6]-naphthyridine derivatives as Syk enzyme inhibitors. The role of the water molecules was explored for the docking based alignment that revealed two conserved water molecules important for proper orientation and alignment of naphthyridine inhibitors in the active site of Syk enzyme. The QSAR model was selected having highest value of Q(2) (0.624) and Pearson-r (0.862). The selected model also displayed the highest values of R(2) (0.978) and F-value (184.5) and the lowest SD (0.862). The contour plots developed on the basis of the best model helped to reveal the essential structural features of naphthyridines derivatives responsible for inhibition of Syk enzyme. The generated model and information revealed from it was utilized to design and predict new congeneric molecules that can be used as potential therapeutic agents.
Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India.
Maninder
M
Kaur
Malkeet Singh
MS
Bahia
Om
O
Silakari
D000255:Adenosine Triphosphate / Q000737:chemistry; D001667:Binding, Competitive; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009287:Naphthyridines / Q000737:chemistry*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D013154:Spleen / Q000201:enzymology; D000072377:Syk Kinase; D014867:Water / Q000737:chemistry*
D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D047428:Protein Kinase Inhibitors; D014867:Water; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase