In order to define the accessibility of the amino acids to some putative external ligand - with a future drug in mind, using the 3D protease structure PDB ID: 1HSG[ 25], we computed the surface accessible to the solvent, using the ASA software [ 51] available at RPBS [ 52], and considered "accessible" all amino acids with an accessibility threshold greater than 25%.
We filtered the results of this exploration to keep only the pairs located on the protein surface as it is the most accessible location for known therapeutic targets (accessibility threshold greater than 25%, using the ASA software [ 26] and implemented by Allan et al. [ 27] based on the 3D PR structure PDB ID 1HSG [ 28] and 3D RT structure PDB ID 1DLO [ 29]).
All AAs having an accessibility threshold greater than 25% are considered "accessible".
For a relative accessibility threshold of 25%, only 46.1% of PPIIDSSP are buried while in the case of turns, β-strands, α-helices and coils, 35.8%, 72.2%, 55.4% and 51.9% of residues are buried, respectively.
A solvent accessibility threshold of 25% was used for classifying residues as exposed or buried.
However, these results also suggest an accessibility threshold, above which enzymatic digestibility does not depend heavily on further pore size expansion.
Using liposomes composed of 10% epi-agisterol in DOPC, we found that epi-agisterol lowers the accessibility threshold to 22.0 25.7 mol % cholesterol in the absence of 25-HC.
To evaluate the influence of the available data in a work position, we used a Q2 index in a two state model with a classical relative solvent accessibility threshold of 16%. Figure S2 shows that, as expected, the level of good predictions increases with the occupancy of a work position and is quite satisfying above 8to1010 members per work position.
If cholesterol-sensing proteins bind only accessible cholesterol, then by lowering the cholesterol-accessibility threshold, 25-HC can increase the sensitivity of these cholesterol-sensing proteins by increasing the fraction of cholesterol available to bind to these proteins.
In liposomes composed of 5%25-HC25-HCand10%gisterol, the cholesterol-accessibility threshold increases to 20.3 25.9 mol %, toward the cholesterol-accessibility threshold established for DOPC.
