File size: 4,985 Bytes
96272bc | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 | #!/usr/bin/env python3
"""
Generate a copy of ddG-backrub.xml that additionally reports per-chain energies.
Why
---
The `unbound_wt` / `unbound_mut` totals in ddG.db3 are whole-pose scores. InterfaceDdGMover
builds the unbound state by rigid-body translating the moving chain(s) 1000 A apart, without
repacking or re-minimizing, and every chain stays in the pose
(protocols/features/InterfaceDdGMover.cc::unbind). So
unbound_X_total = sum over chains of intra(chain) for X in {wt, mut}
and `unbound_mut - unbound_wt` is the summed intramolecular ddG of *every* chain, including
the ones that were never mutated. Those only differ between the wild type and mutant branches
because the whole pose is re-minimized independently in each, so they contribute artifact.
What this adds
--------------
A `TotalEnergyMetric` per chain, reported into ddG.db3 by the same ReportToDB mover that
InterfaceDdGMover already applies to all four states. This is *reporting only* -- it adds no
sampling, consumes no random numbers, and leaves ddG_bind bit-identical (verified against the
unmodified protocol with -constant_seed).
Reading the result
------------------
On the **unbound** states the chains are 1000 A apart, so there are no cross-chain pair
energies and the reported value is exactly that chain's intramolecular energy. That is the
number to use:
per-chain ddG(chain X) = intra_mut(X) - intra_wt(X)
On the **bound** states the value is intra(chain) + roughly half the interface energy, because
Rosetta's residue_total_energies splits each two-body term between its two residues. Those rows
are useful as a cross-check (they sum to the pose total) but should not be read as per-chain
stability numbers.
Caveat this does NOT fix
------------------------
The unbound state is still never relaxed. This gives you the intramolecular strain difference
*in the bound backbone conformation*, not a folding ddG of the free monomer. For that you want
a dedicated monomer protocol (e.g. cartesian_ddg) run on the isolated chain.
"""
import os
def chains_in_pdb(pdb_path):
"""Chain IDs in the order they first appear in the PDB."""
chains = []
with open(pdb_path) as f:
for line in f:
if line.startswith(('ATOM', 'HETATM')):
chain = line[21]
if chain not in chains:
chains.append(chain)
return chains
def write_per_chain_protocol(base_xml_path, chains, out_path, scorefxn='fa_talaris2014'):
"""Write a copy of base_xml_path with a per-chain TotalEnergyMetric for each chain.
Each chain gets its own database table (chain_<X>_energy) with a single `total_energy`
column. Separate tables rather than one table with prefixed columns is deliberate: as of
Rosetta 2022.45, SimpleMetricFeatures builds schema column names as `custom_type + name`
but builds the INSERT as `custom_type + "_" + name`, so any non-empty custom_type produces
"table simple_metrics has no column named ..." at report time.
"""
if not chains:
raise ValueError('No chains given')
# Rosetta lowercases table names, so chains differing only in case would collide.
lowered = [c.lower() for c in chains]
if len(set(lowered)) != len(lowered):
raise ValueError('Chain IDs differ only by case, which collides in table names: %s' % chains)
xml = open(base_xml_path).read()
def substitute(text, anchor, addition):
if anchor not in text:
raise ValueError('Could not find anchor in %s:\n %s' % (base_xml_path, anchor))
return text.replace(anchor, anchor + addition, 1)
selectors = ''.join(
'\n <Chain name="chain_%s" chains="%s"/>' % (c, c) for c in chains)
xml = substitute(
xml, ' <StoredResidueSubset name="restore_neighbor_shell" subset_name="neighbor_shell"/>',
selectors)
metrics = '\n'.join(
' <TotalEnergyMetric name="chain_%s_energy" residue_selector="chain_%s" scorefxn="%s"/>'
% (c, c, scorefxn) for c in chains)
anchor = ' <FILTERS>'
if anchor not in xml:
raise ValueError('Could not find FILTERS block in %s' % base_xml_path)
xml = xml.replace(anchor, ' <SIMPLE_METRICS>\n%s\n </SIMPLE_METRICS>\n\n%s' % (metrics, anchor), 1)
reporters = ''.join(
'\n <SimpleMetricFeatures metrics="chain_%s_energy" table_name="chain_%s_energy"/>'
% (c, c) for c in chains)
xml = substitute(
xml, ' <StructureScoresFeatures scorefxn="%s"/>' % scorefxn, reporters)
with open(out_path, 'w') as f:
f.write(xml)
return out_path
if __name__ == '__main__':
import sys
if len(sys.argv) != 4:
sys.exit('usage: per_chain_protocol.py <base.xml> <input.pdb> <out.xml>')
base_xml, pdb, out = sys.argv[1:4]
found = chains_in_pdb(pdb)
write_per_chain_protocol(base_xml, found, out)
print('Wrote %s with per-chain metrics for chains: %s' % (out, ', '.join(found)))
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