Activity Prediction Database for

Mutants of HIV-1 Protease

The wild-type (wt) amino acid sequence of HIV-1 protease is based on the Protein Data Bank (PDB)1 entry 3phv. The primary sequence of 3phv is given below.
protease sequence

 wt amino acid
 position number
 substitution
 number of  classes (2 or 3)
mutant #1
mutant #2
mutant #3
mutant #4
mutant #5

First choose the wt amino acid residue (1 letter code), the corresponding residue number (1-99), and any one of the 19 possible residue substitutions of the wt residue (1 letter code). Next, choose the number of activity classes (2 or 3). For the two-class case, the activity of a mutant is considered to be either "active" or "inactive". Using three classes, the mutant activity labels are "positive", "intermediate", or "negative". Repeat for up to five single-point mutants of HIV-1 protease. Finally, click on the "Check Activity Levels" button to obtain the predicted activity levels of the requested protease mutants. All predictions are based on decision tree models generated by using residual profile2 vectors for a training set of 536 protease mutants with experimentally measured activity levels. Decision tree models based on the 1-against-all method are used for making the three-class predictions. Among the training set data (those with "known" activity when queried above), the activity levels for 336 of these mutants can be located in Loeb et al.3 The activity of the remaining 200 mutants constitute a currently unpublished personal communication courtesy of Ronald Swanstrom.

References

  1. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N. & Bourne, P. E. (2000). The Protein Data Bank. Nucleic Acids Res. 28, 235-242.
  2. Masso M. & Vaisman I. (2007). Accurate prediction of enzyme mutant activity based on a multibody statistical potential. Bioinformatics, 23, 3155-3161.
  3. Loeb, D. D., Swanstrom, R., Everitt, L., Manchester, M., Stamper, S. E. & Hutchison III, C. A. (1989). Complete mutagenesis of the HIV-1 protease. Nature, 340, 397-400.