The user is able to obtain global scores accounting for the overall
protein propensity as well as for each specific amino acid (seeNote
12 ). As in the A3D-plot, there exists the possibility to select indi-
vidual chains and specific sequence fragments. The central region of
the page is a scrollable table, which agglutinates the scores calcu-
lated for each amino acid and some extra information, such as the
residue number, the 1-letter residue code and the protein chain
where the specific amino acid is placed. Besides, the table can be
resorted, by clicking the top cell of the column. The amino acids
with positive values are colored in clear-yellow, and in this case
buried residues are displayed with an A3Dscore¼0. Usefully, at
this point there exists the possibility to mutate an amino acid or
remutate those changed previously, by clicking the green button
“mutate” and following the instructions mentioned in Subheading
3.2(seeNote 13).3.4.3 Structure It is the most visual interface of A3D (Fig.3c). It projects the
propensity of each individual amino acid upon the 3D protein
surface according to a color code in which blue encodes for solu-
bility and red represents aggregation proneness. The structure is
presented in a 2 s looped motion picture, in which the protein
rotates 360through the vertical axis. Both the 3D coordinates of
the resulting structure and the video can be downloaded as a .pdb
file and in .ogv, .mp4, or.webm formats, respectively (seeNote 14).
If needed, A3D also incorporates the option to manually rotate the
output structure by clicking the “JSmol”button.
3.4.4 Dynamic Mode
Details
Only accessible if the A3D run includes dynamic mode simulations
(Fig.3d), two main objects are displayed; on the one hand, 3D
structures accounting for the initial input structure (blue) and the
most aggregation prone conformation (red) are superposed; on the
other hand, the root mean square deviation (RMSD) of the relative
distances between reciprocal amino acids of the aligned structures is
plotted as a function of the residue number. Both the 3D-structures
and the RMSD values can be downloaded as a .pdb and .csv files,
respectively.äFig. 3(continued) color code as a function of the A3D score, where red is linked to aggregation and blue to
solubility. The black circle highlights the equivalent structural APR from (a). (d) Dynamic details interface. On
the left side, superposition of both the initial (blue) and the most aggregation prone structures (red). On the
right side, the Single Model RMSD profile, in which in the distance between relative amino acids (Yaxis) is
plotted in function of the residue sequence (Xaxis)
Predicting the Aggregation of Protein Structures 435