nsp13 modeling

data/models/6jyt_croll.yml

@@ -0,0 +1,24 @@
+name: "SARS nsp13 helicase 6JYT: ISOLDE refined model"
+pdbids:
+  - 6JYT
+proteins:
+  - Helicase
+organism:
+  - SARS-CoV
+description: >
+  Original model has numerous quite severe (albeit local) problems:
+    * spurious non-proline cis/twisted peptide bonds at A281-282, A285-286, A350-351, A353-354, A439-440, A551-552, B-1-0, B189-190, B206-207, B467-468
+    * high clashscore of 28.7
+    * only 79.6% of residues in favoured portion of Ramachandran plot (should be near 98%)
+    * C-terminal domains (~439 to end) nearly unresolved and severely distorted
+    * Some long loops were modelled despite having no discernable density.
+  Rebuilt well-resolved regions directly into density. Trimmed off unresolved loops. 
+  In the MERS equivalent of this complex (5wwp) the C-terminal domain is well-resolved (but needed 
+  substantial rebuilding in its own right). After rebuilding, I used this (chain A, residues 439 to end)
+  as a reference model (distance and torsion-based) to improve the poorly-resolved C-terminal domains
+  in 6jyt. Given the poor density it cannot be said that these domains are perfect, but application of 
+  the restraints substantially improved both R-factors and geometry.
+url: https://github.com/thorn-lab/coronavirus_structural_task_force/tree/master/pdb/helicase/SARS-CoV/6jyt/isolde
+pdb_url: https://raw.githubusercontent.com/thorn-lab/coronavirus_structural_task_force/master/pdb/helicase/SARS-CoV/6jyt/isolde/6jyt_refine_12.pdb
+creator: Tristan Croll
+rating: 

data/models/helicase_homology_modeling.yml

@@ -0,0 +1,20 @@
+name: GitHub Repo for building an nsp13 / helicase homology model
+description: > 
+  Current structures of the SARS-CoV-2 helicase are limited, and
+  the only structures from other coronaviruses are not ligand bound. To
+  facilitate drug discovery against SARS-CoV-2 helicase, we need to determine a
+  model of the helicase bound to ATP and / or RNA. 
+url: https://github.com/choderalab/nsp13-models
+pdbids: 
+  - 6JYT
+  - 5WWP
+  - 2GK6
+  - 2XZO
+models:
+  - 6jyt_croll
+proteins:
+  - Helicase
+  - Upf1
+creator: Alex Payne
+lab: Chodera lab
+

data/proteins/Upf1.yml

@@ -0,0 +1,8 @@
+protein: Upf1
+organism: human
+name: Regulator of nonsense transcripts 1
+description: >
+  Well-characterized human RNA dependent helicase belonging to the 
+  helicase superfamily 1 (SF1).
+uniprot: https://www.uniprot.org/uniprot/Q92900
+target:  nsp13 helicase activity

data/structures/2GK6.yml

@@ -0,0 +1,7 @@
+pdbid: 2GK6
+proteins:
+  - Upf1 
+targets:
+  - nsp13 helicase activity
+organisms:
+  - human

data/structures/2xzo.yml

@@ -0,0 +1,7 @@
+pdbid: 2XZO
+proteins:
+  - Upf1 
+targets:
+  - nsp13 helicase activity
+organisms:
+  - human

data/structures/5WWP.yml

@@ -0,0 +1,7 @@
+pdbid: 5WWP 
+proteins:
+  - Helicase 
+targets:
+  - nsp13 helicase activity
+organisms:
+  - MERS

data/structures/6JYT.yml

@@ -0,0 +1,7 @@
+pdbid: 6JYT
+proteins:
+  - Helicase 
+targets:
+  - nsp13 helicase activity
+organisms:
+  - SARS-CoV

data/targets/3CLpro_protease_activity.yml

@@ -1,5 +1,5 @@
 target: "3CLpro protease activity"
-name: 3CLpro / Mpro activity
+name: Inhibition of 3CLpro / Mpro activity
 description: >
   3CLpro (main protease, M-PRO, etc) is a viral cysteine protease
   responsible for maturation of the viral polyprotein, necessary for

data/targets/PLpro_protease_activity.yml

@@ -1,4 +1,4 @@
-target: "PLpro protease activity"
+target: PLpro protease activity
 name: Inhibition of PLpro protease activity
 description: >
   PLpro (NSP3, papain-like protease) is a viral cysteine protease

data/targets/host_immune_response.yml

@@ -1,5 +1,5 @@
 target: host immune response
-name: Host immune response
+name: Managing the host immune response
 description: >
   Certain mechanisms allow viruses to avoid host immune response, such as removal of ISG15, a ubiquitin-like protein conjugated to intracellular proteins post interferon activation and involved in cell-to-cell signaling and heightened immune response. Removal of such tags and disruption of signal cascades allow infected cells to avoid apoptotic signals.
 proteins:

data/targets/inhibition_of_nsp13_helicase_activity.yml → data/targets/nsp13_helicase_activity.yml

@@ -1,5 +1,5 @@
 target: nsp13 helicase activity
-name: inhibition of nsp13 helicase activity
+name: Inhibition of nsp13 helicase activity
 description: >
   Nsp13, nonstructural protein 13 has multiple functions with an N-terminal metal binding domain (MBD) and a helicase domain (Hel). The nsp13 SARS sequence is conserved and helicase activity is necessary for COVID replication. While this is an attractive target for viral inhibition, there are few reports on nsp13 inhibitors. Helicase inhibition has been used for virus (HSV-amenavir) and cancer treatment (eIF41, RocA rocaglamides), but likely due to its inherent flexibility, inhibitor design is challenging and high throughput screen hits are generally DNA binding artifacts.
 proteins:

schema/validation.py

@@ -49,6 +49,7 @@ class ValidProteins(str, Enum):
     E_protein = 'E protein'
     PD_1 = 'PD-1'
     virion = "virion"
+    Upf1 = "Upf1"
 
 
 class ValidDomains(str, Enum):
@@ -71,12 +72,14 @@ class ValidTargets(str, Enum):
     viral_fusion = 'viral fusion'
     host_immune_response = 'host immune response'
     cell_cyle_inhibitors = 'cell cycle inhibitors'
+    nsp13_helicase_activity = 'nsp13 helicase activity'
 
 
 class ValidOrganisms(str, Enum):
     human = 'human'
     sars_cov = 'SARS-CoV'
     sars_cov_2 = 'SARS-CoV-2'
+    mers = 'MERS'
 
 
 class ResourcesEnum(str, Enum):