top7 readme

Author: jaumebonet

03.experimental/top7/README.ipynb

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+
+
+```python
+# Default Libraries
+import os
+import StringIO
+
+# External Libraries
+import pandas as pd
+import numpy as np
+import matplotlib
+import matplotlib.pyplot as plt
+import seaborn as sns
+import networkx as nx
+from IPython.display import FileLink, FileLinks
+
+# Own Libraries
+import rstoolbox  # Learn about this library at: http://lpdi-epfl.github.io/RosettaSilentToolbox
+
+import readme
+
+# Global Parameters
+plt.rcParams['svg.fonttype'] = 'none'
+rstoolbox.utils.format_Ipython()
+```
+
+
+
+
+<style>
+table.dataframe {
+    font-family: monospace;
+}
+</style>
+
+
+
+# Design of a RSVF site IV carrier from TOP7
+
+> This summary does not track all attempts and variations, just the pathway towards obtaining the designs that were experimentally characterized.
+
+
+```python
+# Direct information obtain from scoring TOP7 with Rosetta
+baseline = rstoolbox.io.get_sequence_and_structure(os.path.join('selection', 'baseline', '1qys.pdb'))
+baseline
+```
+
+
+
+
+<div>
+<style scoped>
+    .dataframe tbody tr th:only-of-type {
+        vertical-align: middle;
+    }
+
+    .dataframe tbody tr th {
+        vertical-align: top;
+    }
+
+    .dataframe thead th {
+        text-align: right;
+    }
+</style>
+<table border="1" class="dataframe">
+  <thead>
+    <tr style="text-align: right;">
+      <th></th>
+      <th>score</th>
+      <th>fa_atr</th>
+      <th>fa_rep</th>
+      <th>fa_sol</th>
+      <th>fa_intra_rep</th>
+      <th>fa_intra_sol_xover4</th>
+      <th>lk_ball_wtd</th>
+      <th>fa_elec</th>
+      <th>pro_close</th>
+      <th>hbond_sr_bb</th>
+      <th>hbond_lr_bb</th>
+      <th>hbond_bb_sc</th>
+      <th>hbond_sc</th>
+      <th>dslf_fa13</th>
+      <th>omega</th>
+      <th>fa_dun</th>
+      <th>p_aa_pp</th>
+      <th>yhh_planarity</th>
+      <th>ref</th>
+      <th>rama_prepro</th>
+      <th>time</th>
+      <th>description</th>
+      <th>sequence_A</th>
+      <th>structure_A</th>
+      <th>phi_A</th>
+      <th>psi_A</th>
+    </tr>
+  </thead>
+  <tbody>
+    <tr>
+      <th>0</th>
+      <td>191.625</td>
+      <td>-498.177</td>
+      <td>194.188</td>
+      <td>320.719</td>
+      <td>1.444</td>
+      <td>19.121</td>
+      <td>-7.686</td>
+      <td>-112.63</td>
+      <td>0.0</td>
+      <td>-29.587</td>
+      <td>-31.008</td>
+      <td>-2.424</td>
+      <td>-4.577</td>
+      <td>0.0</td>
+      <td>0.935</td>
+      <td>296.765</td>
+      <td>-8.478</td>
+      <td>0.0</td>
+      <td>22.146</td>
+      <td>30.876</td>
+      <td>2.0</td>
+      <td>1qys_0001</td>
+      <td>DIQVQVNIDDNGKNFDYTYTVTTESELQKVLNELKDYIKKQGAKRVRISITARTKKEAEKFAAILIKVFAELGYNDINVTFDGDTVTVEGQL</td>
+      <td>LEEEEEEEELLLLEEEEEEEELLLLHHHHHHHHHHHHHHHHLLLEEEEEEELLLHHHHHHHHHHHHHHHHHLLLLEEEEEEELLEEEEEEEL</td>
+      <td>[0.0, -91.4576, -100.939, ...]</td>
+      <td>[-165.465, 111.061, 116.221, ...]</td>
+    </tr>
+  </tbody>
+</table>
+</div>
+
+
+
+## Generation of fragments to guide the folding process
+
+Structure-based fragments to guide the folding were generated applying the RosettaScript [mkfragments](design/mkfragments.xml) to `1QYS`, the PDB containing **TOP7**.
+
+## Making the designs
+
+The construction of the **TOP7**-derived designs implies the grafting to RSVF's site IV epitope with the presence of its neutralizing antibody 101F [motif.pdb](design/motif.pdb).
+
+The process is split in several steps.
+
+### Folding
+
+Site IV was grafted into **TOP7** by means of the _NubInitioMover_ with the RosettaScript [ffl.xml](design/ffl.xml) into a [SLURM](https://slurm.schedmd.com/)-based cluster through the submiter script [submit_ffl.sh](design/submit_ffl.sh).
+
+A total of 800 decoys were generated without allowing for any sequence mutation to the template residues. The aim of this firts run was to explore and find a folded conformation that would:
+
+* carry and stabilize at backbone lever site IV.
+* fold back to a conformation close to **TOP7** keeping the proper beta pairing.
+* shift enought the conformation to be productive in presenting site IV to 101F (avoid clashes).
+
+From all the decoys, [87_ffl_twostrand_1qys_Lys_0001](design/87_ffl_twostrand_1qys_Lys_0001.pdb) was selected as seed for the next step of the process. The values of this decoy in the context of the design population are marked with a red line.
+
+
+```python
+step1 = rstoolbox.io.parse_rosetta_file('design/top7_ffl_folding.minisilent.gz')
+readme.plot_step1(step1)
+```
+
+
+![png](README_files/README_4_0.png)
+
+
+### Full Design
+
+Full design was carried out applying to [87_ffl_twostrand_1qys_Lys_0001](design/87_ffl_twostrand_1qys_Lys_0001.pdb) the RosettaScript [design_full.xml](design/design_full.xml) submited via the SLURM script [submit_design_full.sh](design/submit_design_full.sh), generating a total of 92 designs from which [sd_top7_12top7_graft_0001](design/sd_top7_12top7_graft_0001.pdb) (highlighted in red in the distributions) was selected.
+
+
+```python
+fulldes = rstoolbox.io.parse_rosetta_file('design/sd_top7_', {'sequence': 'P'})
+readme.plot_full(fulldes)
+```
+
+
+![png](README_files/README_6_0.png)
+
+
+### Part Design
+
+Partial design was carried out applying to [87_ffl_twostrand_1qys_Lys_0001](design/87_ffl_twostrand_1qys_Lys_0001.pdb) the RosettaScript [design_part.xml](design/design_part.xml) submited via the SLURM script [submit_design_part.sh](design/submit_design_part.sh), generating a total of 100 designs from which [sd_top7_nterm2_45top7_graft_0002](design/sd_top7_nterm2_45top7_graft_0002.pdb) (highlighted in red in the distributions) was selected.
+
+
+```python
+partdes = rstoolbox.io.parse_rosetta_file('design/sd_top7_nterm2_', {'sequence': 'P'})
+readme.plot_part(partdes)
+```
+
+
+![png](README_files/README_8_0.png)
+
+
+### Remodel and Resurface
+
+Both selected designs were submited to REMODEL to shorten the first loop of the structure and fix surface residues in order to improve the quality of the decoys, yielding the final two designs as described in the paper.
+
+
+```python
+designs = readme.load_experimental()
+readme.data_plot(designs)
+```
+
+
+![png](README_files/README_10_0.png)
+