Peptides Design Based on the Interfacial Helix of Integrase Dimer

Author

Kong, R. ; Wang, C.X. ; Ma, X.H. ; Liu, J.H. ; Chen, W.Z.

Author_Institution

Coll. of Life Sci. & Bioeng., Beijing Univ. of Technol.

fYear

2006

Firstpage

4743

Lastpage

4746

Abstract

HIV-I integrase (IN) plays a crucial role in the retroviral life cycle. The peptides derived from the helix of IN were reported to have the potency of inhibition. We designed a series of peptides based on interface helices alpha1 and alpha5 with the aim of increasing their inhibitory activity. The helix-forming tendency and the affinity with IN were essential for interfacial peptide inhibitors. The MD simulation and AGADIR prediction both showed favorable results for the designed peptides. The binding mode and binding free energy of peptide and IN were investigated subsequently to test our design. The improvement in binding free energy compared with that of alpha1 and alpha5 indicates that some of the designed peptides may have a higher potency for inhibiting the dimerization of IN. This study provides some useful information for rational design of IN peptide inhibitor

Keywords

association; biochemistry; enzymes; free energy; molecular biophysics; molecular dynamics method; physiological models; AGADIR prediction; HIV-I integrase; MD simulation; alpha1 helix; alpha5 helix; binding free energy; binding mode; dimerization; helix-forming tendency; integrase dimer; interfacial helix; interfacial peptide inhibitors; peptides; retroviral life cycle; Biochemistry; Biomedical engineering; DNA; Educational institutions; Genomics; Human immunodeficiency virus; Inhibitors; Peptides; Predictive models; Testing;

fLanguage

English

Publisher

ieee

Conference_Titel

Engineering in Medicine and Biology Society, 2005. IEEE-EMBS 2005. 27th Annual International Conference of the

Conference_Location

Shanghai

Print_ISBN

0-7803-8741-4

Type

conf

DOI

10.1109/IEMBS.2005.1615531

Filename

1615531