Book of Abstracts: Albany 2007
June 19-23 2007
3D Structure Model for a Peptide Presenting the Immunogenic Crown of the HIV-1 GP120 V3 Loop
The high-resolution 3D structure model of a peptide (?CRK?) offering the immunogenic crown of the HIV-1 V3 loop was built by computer modeling in terms of NMR spectroscopy data (1). Using the CONFNMR-2 program (2) combined with the TINKER software tools for molecular design (3), CRK was found to reveal in water the properties characteristic of metastable peptide, which gives rise to the prevalent structure located in the deep potential well on the energy peptide surface and consistent with NMR data (1). In this best energy structure presented in the Figure, the peptide of interest displays the quasi-cyclic spatial fold and its central immunogenic crest Gly-Pro-Gly-Arg-Ala-Phe makes the double β-turn close to the one observed in the X-ray structure for the V3 peptides bound to neutralizing antibodies (4). The presence in the ensemble of the simulated structures of only one low-energy conformation matching the experimental data, allows us to suggest that this particular structure operates as the conformation responsible for CRK binding with antibodies. This assumption is confirmed by the results derived from the flexible molecular docking of the simulated structure to the X-ray conformation of the Fab-fragment of antibody 59.1 (4). These results point to the possibility of the stable ?antigen-antibody? complex formation that causes substantial changes neither in the spatial peptide fold nor in the conformations of its individual amino acid residues.
Figure: 3D CRK structure computed on the basis of NMR spectroscopy data (1).
We are grateful for financial support by the Belarusian Foundation for Basic Researches (project No X06-020).
References and Footnotes
Alexander M. Andrianov*
*Institute of Bioorganic Chemistry