Fig 5.

In silico estimation of the impact on protein stability of CTL escape mutations in HIV-1B Gag p17 and p24. (A) Protein stability is defined by the difference in Gibbs free energy (ΔG) between the unfolded and folded states. The FOLDEF energy function (51) was used to estimate the ΔG for the “wild-type” (WT) protein sequence and for each CTL escape mutant sequence (MUT), and the stability impact of a mutation was quantified as the absolute value of the difference between WT ΔG and MUT ΔG (|ΔΔG|). (B) The impact on protein stability (|ΔΔG|) was estimated for the 21 classical CTL escape mutations located within the Gag p17 trimer and p24 pentamer and hexamer crystal structures. (C) The CTL escape-associated impact on protein stability (|ΔΔG|) and reduction in replication capacity (RC) were negatively correlated when the outlier p24 R264K mutation was excluded from the analysis (rho = −0.46, P = 0.02; Spearman rank correlation). CTL escape mutations in Gag p17 and p24 are denoted by circles and triangles, respectively.