Comparative bioinformatic analysis of the conserved domains, amino acid residues, and binding grooves of tumor necrosis factor.
OBJECTIVE
Comparative structural bioinformatic analysis of the conserved domains and amino acid residues, binding grooves of the tumor necrosis factor (TNF)α and β in order to elucidate structurebased inhibitor development was conducted.


METHODS
We carried out the bioinformatics study of TNF proteins at the Department of Bio-informatics (Galgotias University, India) between June and December 2012. TNFα and TNF-β functional protein sequences in FASTA format were obtained from the NCBI database for analysis. The online tool ClustalW from the European Bioinformatic Institute was used for multiple sequence alignment to record similarities. The Jmol server was used for 3D visualization of alpha helix, beta sheet and loops of TNF proteins. The PyMOL molecular visualization system was used to generate surface cavity and to identify binding grooves of TNF proteins.


RESULTS
This study showed highly conserved amino acids residues such as LYS11, PRO12, ALA14, HIS15, VAL50, PRO51, GLY54, LEU55, TYR56, LEU57, TYR59, SER60, GLN61, GLY122, VAL123, PHE124, PHE152, and GLY153 are consequent amino acids in TNF-β while residues such as ALA31, HIS32, SER77, GLN78, PHE166, and GLY167 are consequent amino acids in TNF-β. Surface cavity and binding grooves showed TNF-β with larger surface cavities than TNF-α with higher chances for drug development since small drug-like molecules can bind easily into the groove.


CONCLUSIONS
The results illustrate the structure of TNF proteins and the novel findings may guide future research on TNF and in the process of assisting the optimization of the pharmacological properties involving the two crucial proteins.
1Department of Bio-informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, India, 2 College of Pharmacy and Health Care, Tajen University, Yanpu, Taiwan.
Chiranjib
C
Chakraborty
Govindasamy
G
Agoramoorthy
D000596:Amino Acids; D001665:Binding Sites; D019295:Computational Biology; D008233:Lymphotoxin-alpha; D017434:Protein Structure, Tertiary; D014409:Tumor Necrosis Factor-alpha
D000596:Amino Acids; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha