Figure S1: The probability pD that the HIV-1-PR monomer is in its denatured state as a function of Monte Carlo steps for the monomerincubated together with peptide 83-92 (red open squares), 24-34 (green filled circles) and 4-13 (black open circles) at room temperature (T=24oC).
Figure S2: The probability distribution of the RMSD for the protease monomer alone (blue triangles) and incubated with peptide 83-92 (red open squares), 24-34 (green filled circles) and 4-13 (black open circles) at T=44oC (top panel) and T=24oC (bottom panel).
Figure S3: The average radius of gyration of monomeric protease in the denatured state for the protein alone (blue triangles) and incubated with peptide 83-92 (red open squares), 24-34 (green filled circles) and 4-13 (black open circles), as a function of the temperature.
Figure S4: (upper diagonal) the contact map associated with the state of HIV-1-PR monomer denatured by peptide 83-92 at T=24oC. Darker symbols indicate high contact probability, lighter symbols indicate low contact probability. (lower diagonal) the contact map of the native conformation.
Figure S5: the free energy (in kJ/mol) at T=44oC calculated from the Monte Carlo simulations for the protease alone as a function of the overall RMSD of the protein and of the RMSD associated with segments 83-92 and 24-34 of the protein.
Figure S6: The probability that peptide 24-34 is bound to peptide 83-92 in simulations carried out at different temperatures. Black solid circles correspond to simulation A where peptide 24-34 is flexible, while red empty squares correspond to simulation B where peptide 24-34 is assumed to be rigid. The dashed curve is a fit obtained with the two-state model of Eq. (6), giving a χ2=2 10-3.
Figure S7: Peptide concentration dependence of the bindin probability (top panel) and that of finding the protein in its denatured state (bottom panel), respectively, for the monomercomplexed with peptide 83-92 at T=24oC (pink dotted curves), T= 44oC (red solid curves) and T= 59oC (green dashed curves). The squares correspond topb and pDat the fixed concentration of 1.66 mM and for each of the temperatures at which the numerical simulations were carried out.
Figure S8: If peptide 83-93 is mutated, changing its interaction energy Eppto the protein of a quantity Δε, the associated kI can be obtained substituting Eq. (2a) in Eq. (8), obtaining
,
which is displayed in the above figure.
The probabilities that, respectively, the peptide is bound to the protein and the protein is denatured can be written as
(S1)
which is formally equivalent to a bimolecular, whose probability is
(S2)
whereΔE is the binding energy.
A tentative definition of inhibition constant for a system which includes the four states defined in the Eq. 1 in the main text would give
,(S3)
which is not concentration independent.