Molecular dynamics simulation studies and in vitro site directed mutagenesis of avian beta-defensin Apl_AvBD2.

BMC Bioinformatics
Soja Saghar SomanE Sreekumar

Abstract

Defensins comprise a group of antimicrobial peptides, widely recognized as important elements of the innate immune system in both animals and plants. Cationicity, rather than the secondary structure, is believed to be the major factor defining the antimicrobial activity of defensins. To test this hypothesis and to improve the activity of the newly identified avian beta-defensin Apl_AvBD2 by enhancing the cationicity, we performed in silico site directed mutagenesis, keeping the predicted secondary structure intact. Molecular dynamics (MD) simulation studies were done to predict the activity. Mutant proteins were made by in vitro site directed mutagenesis and recombinant protein expression, and tested for antimicrobial activity to confirm the results obtained in MD simulation analysis. MD simulation revealed subtle, but critical, structural variations between the wild type Apl_AvBD2 and the more cationic in silico mutants, which were not detected in the initial structural prediction by homology modelling. The C-terminal cationic 'claw' region, important in antimicrobial activity, which was intact in the wild type, showed changes in shape and orientation in all the mutant peptides. Mutant peptides also showed increased solvent ac...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Feb 8, 1997·Lancet·R E Hancock
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Aug 4, 2001·The Journal of Biological Chemistry·D M HooverJ Lubkowski
Jan 25, 2002·Nature·Michael Zasloff
Oct 18, 2002·Antimicrobial Agents and Chemotherapy·Margareta StarkCharles M Deber
Mar 5, 2003·Pharmacological Reviews·Michael R Yeaman, Nannette Y Yount
Feb 3, 2004·Current Medicinal Chemistry·Dina Schneidman-DuhovnyHaim J Wolfson
Jul 27, 2005·The Journal of Biological Chemistry·Evgenia GlukhovCharles M Deber
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Feb 24, 2006·Journal of Peptide Science : an Official Publication of the European Peptide Society·Enno KlüverAxel Schulz
Jul 19, 2006·Clinical Microbiology Reviews·Håvard JenssenRobert E W Hancock
Jan 27, 2007·BMC Bioinformatics·Anita Suresh, Chandra Verma

❮ Previous
Next ❯

Citations

Feb 13, 2013·Journal of Biomedical Semantics·Toshiaki KatayamaToshihisa Takagi
Mar 6, 2012·Journal of Peptide Science : an Official Publication of the European Peptide Society·Deying MaShengwang Liu
Feb 26, 2016·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Haitham A YacoubAhmed M Elazzazy
May 7, 2013·Developmental and Comparative Immunology·Tryntsje CuperusHenk P Haagsman
Jun 21, 2016·Journal of Molecular Biology·Saumya BajajManidipa Banerjee
Jan 12, 2019·Journal of Biomolecular Structure & Dynamics·Kullappan MalathiSudha Ramaiah
Mar 17, 2012·Science Translational Medicine·Nicholas P TatonettiRuss B Altman

❮ Previous
Next ❯

Datasets Mentioned

BETA
AY641439

Software Mentioned

PyMol
GROMACS
BLAST
Clustal W
MODELLER
PROSA2003
XMGRACE
PSI
SymmDock

Related Concepts