Star-shaped conformers generated by co-evolutionary docking predict cross-fitting glycoprotein trimer pre-fusion interfaces on VHSV fish rhabdovirus

gpGVHSV from 89 amino acid sequences of different isolates from diverse sources were aligned by Clone Manager vs9. The 67EFEDIN and 302LNHLIT amino acid sequences around the R4-linker and the TrD were in bold red letters. Only one (I71T) or three (N203G) mutations (isolates in red), respectively were detected.

Contains small star-shaped tripartite molecules manually designed by 2D drawing different central atoms / rings and sizes and 3-6 carbon arms ended by alanines. The designed 2D molecules were manually drawn in MolSoft. To conserve their 2D geometries during ADV docking, optimal conformers were generated by the DW / mmff94s+ force-field algorithm31 The best ADV conformer docking to gpGVHSV R4-TrD interface contacting all the A,B,C chains of the trimer, was conformer number 30 (cn30). The cn30 conformer was input parent and cavity for DWBEL co-evolution. Files * .dwar can be opened in DW, freely available at https://openmolecules.org/datawarrior/download.html

This *.dwar DW tables contain 549 top-3D conformers selected by their ADV affinities by 4-runs. The table is provided with threshold slider-filters to their DW_BEL and ADV docking-scores, Molecular weights and logP properties, to select for particular threshold combinations. Files *.dwar can be opened in DW, freely available at https://openmolecules.org/datawarrior/download.html

To compare the cavities preferentially targeted by thousands of new children-conformers, the percentages of docked cavities in gpGVHSV were approximated with the PyMol-Python script nearby11.py. The different gpGVHSV cavities were defined by their three most characteristic amino acids as: Bc (around the bottom-cavity at the end of the TrD helix) = 317D and/or 320S and/or 335K, R4-TrD (around the R4-TrD α-helix interface) = 67E and/or 304H and/or 307T and Sc (around the trimer side-cavities) = 296T and/or 366S and/or 411Y. The script calculated the percentages by the formula, 100 * number of children in each virtual cavity / total numbers of children docked. Copy all files into the same directory ( *.py, gpGVHSV and output_number.pdbqt). Open the gpGVHSV file in PyMol and load the Python script by PyMol/File/Run Script/*.py.

PyMol-Python script to extract the ADV-conformer row data of the 3313.sdf file (including their DWBEL and ADV affinities) corresponding to Bc and R4-TrD txt files with the NN numbered conformers classified by their targeting to each of the cavities calculated by nearby11.py.