Methods

Docking

The Human Annexin under the PDB code 1AIN is the docked protein. The ligands are classified as seq1 and seq2 type, being always seq2 smaller than seq1 and prefixing it. We used the tool GOLD \cite{Jones_1997}, available through the software Cambridge Structural Database System (CSDS), to simulate poses among the enzyme and ligands (peptides). GOLD ranked the ten better dockings of all ligands. We selected the pose with the lowest free energy from each ligand as evidence of successful experimental results concerning the enzyme and ligands. All ligands docked with the smallest free energy are of the seq2 type. Considering GOLD do not accept as entry unfolded ligands, we also created folded structures via the PEP-FOLD version 2.0 \cite{Thévenet2012}. It was not possible to use the PEP-FOLD version 3.0, since, until the current date, it was not accepting as input a disulfide bond definition present on all ligands between positions 2 and 10. We added hydrogens to the protein and ligands for successful docking simulation. We use GOLD native functions to add hydrogens from the enzyme and OPEN BABEL software \cite{O_Boyle_2011} for the same purpose with ligands, besides converting the PDB file format of ligands delivered from PEP-FOLD to MOL file format. The conversion of ligands from PDB to MOL file format was necessary since GOLD does not simulate docking using two PDB file formats. Although we made the docking simulation in a Linux OS, the GOLD high definition images from atoms contact were created using an MS Windows OS, due to the Linux OS MESA drivers always crashing on trying to render high-resolution pictures of enzyme-ligand poses. We provide the surface image of the enzyme docked with its better ligand using Chimera software\cite{Pettersen_2004}.

Acknowledgment

Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081).