Book of Abstracts: Albany 2003
June 17-21 2003
Immunoreactive Conformation of the Principal Neutralization Site of Minnesota HIV-1 Isolate
A hierarchical procedure (1), using a ?bottom-up? strategy and combining (i) a probabilistic approach for estimating all possible starting structures, (ii) restrained molecular mechanics algorithms for selection of all energetically prefered conformers, as well as (iii) quantum chemical computations for refining their geometry, was used to study the structural properties of the HIV-MN neutralizing epitope in terms of NMR spectroscopy data (2). As a result, only one of initial structures matching the experimental and theoretical data was found to be well-ground for implementing the function of immunoreactive conformation of the virus immunogenic crown. The geometric parameters of this structure in water solution were shown to correspond to a double β-turn conformation similar to that revealed in crystall for synthetic molecules imitating the central region of the HIV-MN V3 loop. The following conclusion was drawn from the comparative analysis of simulated structure with the one computed in study (3): the HIV-MN immunogenic tip has some inherent conformational flexibility that manifests at the alterations of microenvironmental conditions and leads to the structural transitions changing the local conformation of the stretch of interest but retaining its spatial main chain fold. On the basis of all data obtained, the high resolution 3D structure model for the HIV-MN principal neutralization site was constructed, and its geometric parameters were compared with the corresponding characteristics of conformers derived earlier (4) for describing the conformational features of immunogenic tip of gp120 from Thailand HIV-1 isolate.
The results are discussed in the light of literature data on HIV-1 neutralizing epitope structure.
This work was supported by grant from the Byelorussian Foundation of Fundamental Investigations (X01-066).
Alexander M. Andrianov*
Institute of Bioorganic Chemistry