Book of Abstracts: Albany 2007
June 19-23 2007
Computing the Invariant Structure Elements for the Principal Neutralizing Determinant of the Human Immunodeficiency Virus Type 1
The objective of the present study was to compute the 3D structures of the principal neutralizing determinant of the human immunodeficiency virus type 1 (V3 loop of the gp120 protein) in the HIV-MN and HIV-Haiti isolates as well as to compare their conformational characteristics with the purpose of determining the structure elements common for two virus modifications. To this end, the computer approaches, that combined the NMR-based methods of 3D protein structure modeling with the mathematical statistics methods, were used. As a result, the V3 loop secondary structures and the conformations of its irregular segments were analyzed for the HIV-MN and HIV-Haiti strains in water and the collation of the simulated structural models was implemented followed by defining the conservative structure elements of this functionally important site of gp120. The variability of the amino acid sequence was found to stimulate the considerable structural rearrangements of the V3 loop. However, the greater part of its amino acid residues was shown to preserve the conformations in the virus strains of interest. The invariant structure elements of V3 appearing in the functionally significant regions of gp120 are considered as the promising targets for potential drugs. The search for them may be realized by the molecular docking methods with posterior selecting the chemical compounds suitable as a basis for design of the safe and effective antiviral agents.
The implications are discussed in conjunction with the data of my recent papers (1, 2) devoted to determining the structure elements recurring within the HIV-1 V3 loop regardless of its environment and sequence variability.
I am 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