Solution structure of a putative HIV1 immunogenic peptide: computer simulation of the principal CD4 binding domain of...

A 15-residue segment within the principal CD4 binding domain of gp120 from HIV1 is a natural subject for vaccine development. Knowledge of a three-dimensional structure of this peptide in aqueous solution can in principle be used for pharmacophoric footprint identification. However, the peptide is resistant to structural characterization using nuclear magnetic resonance (NMR) due to aggregation properties. Here we examine the conformational properties of the peptide using molecular dynamics simulation. Three simulations were performed starting from widely different structures of the peptide determined by NMR in organic solvents. The three structures converge during the simulations to a common structure in both Cartesian and in backbone dihedral conformational space. Preliminary examination of the average three-dimensional structure identifies, after sequence threading, characteristics of potential use as a pharmacophoric footprint.