Modeling parametersa

gp120 positionIntroduced changebΔ volc3)Modeled orientationdComment
chi1, degrees (rmsd)chi2, degrees (rmsd)Observed % (optimal angles)
112W/A−97Removes stabilizing interaction with Trp 427
255V/W58110 (3.5)−89 (0.0)20.7 (65°, −89°)2.6-Å close contact with Trp 112 ring
257T/A−26Removes stabilizing H-bond with 370 carbonyl
273R/W15−58 (2.3)−73 (1.9)6.9 (−73°, −88°)Clashes with Gln 287, which can be easily resolved; ring makes H-bond with 233 carbonyl and stacking interactions with Tyr 484 across domain interface
375S/W9098 (2.5)−84 (1.0)20.7 (65°, −84°)2.5-Å clash with Thr 257 side chain
S/F62110 (3.7)91 (0.0)21.3 (66°, 91°)
S/Y68110 (5.0)89 (0.0)15.0 (63°, 89°)Reducing chi1 results in clash with Thr 257
377N/L28−165 (0.0)133 (1.0)4.8 (−165°, 168°)Good van der Waals contacts made with Phe 210 and Leu 116, stabilizing domain interface
423I/P−34Backbone phi needs to change roughly 30° to accommodate
423I/M0Triple mutation enhances calculated helix-forming
425N/K39    propensity of β20 strand
447S/I5175 (2.6)−131 (4.0)16.1 (62°, 164°)van der Waals contacts with Ile 261 and 262 sugar
481S/F62−173 (0.7)79 (0.0)25.0 (−179°, 79°)Clash with Gln 287, which can easily move; van der Waals contacts with Ile 285 and aliphatic base of 287 across domain interface
  • a The modeling was carried out with the YU2 gp120 core:D1D2 CD4:17b Fab complex (PDB accession code 1G9N). Residue numbers correspond to those of the prototype HXBc2 HIV-1 strain, as per current convention (37).

  • b The amino acids are given in single-letter code. The amino acid residue in the wild-type YU2 gp120 is written first, followed by the substituted amino acid residue.

  • c The change in volume associated with the amino acid substitution was calculated based on the volume enclosed by the van der Waals radii, using the atomic volumes provided by F. M. Richards (70).

  • d Modeling was performed as described in Materials and Methods, using the experimentally determined side chain rotamer classes specified by Ponder and Richards (66). Modeled rotamers are specified by the percentage of the observed side chains that fall into a particular rotamer class (observed percent) and the optimal chi1/chi2 angles which indicated the observed optimal rotamer orientation for that particular class. The chi1 and chi2 values listed in the table are those that resulted in minimal steric clash while being close to a particular rotamer optimum. The root mean square deviation (rmsd) values represent the deviation of the modeled chi1/chi2 angles from the observed optimum values.