From 7569c2cc69c50dcd539483a100b77dfc5509f1d8 Mon Sep 17 00:00:00 2001
From: Gabriel Studer <gabriel.studer@unibas.ch>
Date: Wed, 3 Apr 2024 08:45:17 +0200
Subject: [PATCH] dockq: enable parameterization for peptides as recommended by
CAPRI
---
modules/mol/alg/pymod/dockq.py | 39 ++++++++++++++++---
modules/mol/alg/tests/CMakeLists.txt | 1 +
modules/mol/alg/tests/test_ost_dockq.py | 51 +++++++++++++++++++++++++
3 files changed, 85 insertions(+), 6 deletions(-)
create mode 100644 modules/mol/alg/tests/test_ost_dockq.py
diff --git a/modules/mol/alg/pymod/dockq.py b/modules/mol/alg/pymod/dockq.py
index 2db14d1f6..e8ec3f7a5 100644
--- a/modules/mol/alg/pymod/dockq.py
+++ b/modules/mol/alg/pymod/dockq.py
@@ -154,7 +154,8 @@ def _ContactScores(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2,
return (nnat, nmdl, fnat, fnonnat)
-def _RMSDScores(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2, dist_thresh=10.0):
+def _RMSDScores(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2, dist_thresh=10.0,
+ cb_mode=False):
# backbone atoms used for superposition
sup_atoms = ['CA','C','N','O']
@@ -173,8 +174,11 @@ def _RMSDScores(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2, dist_thresh=10.0):
# iRMSD
#######
- int1 = ref.Select(f"cname={mol.QueryQuoteName(ref_ch1)} and {dist_thresh} <> [cname={mol.QueryQuoteName(ref_ch2)}]")
- int2 = ref.Select(f"cname={mol.QueryQuoteName(ref_ch2)} and {dist_thresh} <> [cname={mol.QueryQuoteName(ref_ch1)}]")
+ i_ref = ref
+ if cb_mode:
+ i_ref = ref.Select("aname=CB or (rname=GLY and aname=CA)")
+ int1 = i_ref.Select(f"cname={mol.QueryQuoteName(ref_ch1)} and {dist_thresh} <> [cname={mol.QueryQuoteName(ref_ch2)}]")
+ int2 = i_ref.Select(f"cname={mol.QueryQuoteName(ref_ch2)} and {dist_thresh} <> [cname={mol.QueryQuoteName(ref_ch1)}]")
ref_pos = geom.Vec3List()
mdl_pos = geom.Vec3List()
for r in int1.residues:
@@ -263,7 +267,8 @@ def _DockQ(fnat, lrmsd, irmsd, d1, d2):
return (fnat + _ScaleRMSD(lrmsd, d1) + _ScaleRMSD(irmsd, d2))/3
def DockQ(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2,
- ch1_aln=None, ch2_aln=None):
+ ch1_aln=None, ch2_aln=None, contact_dist_thresh = 5.0,
+ interface_dist_thresh = 10.0, interface_cb = False):
""" Computes DockQ for specified interface
DockQ is described in: Sankar Basu and Bjoern Wallner (2016), "DockQ: A
@@ -294,6 +299,25 @@ def DockQ(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2,
The first sequence must match the sequence in *ref_ch2* and
the second to *mdl_ch2*.
:type ch2_aln: :class:`ost.seq.AlignmentHandle`
+ :param contact_dist_thresh: Residues with any atom within this threshold
+ are considered to be in contact. Affects contact
+ based scores fnat and fnonnat. CAPRI suggests
+ to lower the default of 5.0 to 4.0 for
+ protein-peptide interactions.
+ :type contact_dist_thresh: :class:`float`
+ :param interface_dist_thresh: Residues with any atom within this threshold
+ to another chain are considered interface
+ residues. Affects irmsd. CAPRI suggests to
+ lower the default of 10.0 to 8.0 in
+ combination with interface_cb=True for
+ protein-peptide interactions.
+ :type interface_dist_thresh: :class:`float`
+ :param interface_cb: Only use CB atoms (CA for GLY) to identify interface
+ residues for irmsd. CAPRI suggests to enable this
+ flag in combination with lowering
+ *interface_dist_thresh* to 8.0 for protein-peptide
+ interactions.
+ :type interface_cb: :class:`bool`
:returns: :class:`dict` with keys nnat, nmdl, fnat, fnonnat, irmsd, lrmsd,
DockQ which corresponds to the equivalent values in the original
DockQ implementation.
@@ -301,8 +325,11 @@ def DockQ(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2,
_PreprocessStructures(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2,
ch1_aln = ch1_aln, ch2_aln = ch2_aln)
nnat, nmdl, fnat, fnonnat = _ContactScores(mdl, ref, mdl_ch1, mdl_ch2,
- ref_ch1, ref_ch2)
- irmsd, lrmsd = _RMSDScores(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2)
+ ref_ch1, ref_ch2,
+ dist_thresh = contact_dist_thresh)
+ irmsd, lrmsd = _RMSDScores(mdl, ref, mdl_ch1, mdl_ch2, ref_ch1, ref_ch2,
+ dist_thresh = interface_dist_thresh,
+ cb_mode = interface_cb)
return {"nnat": nnat,
"nmdl": nmdl,
"fnat": fnat,
diff --git a/modules/mol/alg/tests/CMakeLists.txt b/modules/mol/alg/tests/CMakeLists.txt
index 268d09c81..e1a1aaf82 100644
--- a/modules/mol/alg/tests/CMakeLists.txt
+++ b/modules/mol/alg/tests/CMakeLists.txt
@@ -13,6 +13,7 @@ set(OST_MOL_ALG_UNIT_TESTS
test_stereochemistry.py
test_contact_score.py
test_biounit.py
+ test_ost_dockq.py
)
if (COMPOUND_LIB)
diff --git a/modules/mol/alg/tests/test_ost_dockq.py b/modules/mol/alg/tests/test_ost_dockq.py
new file mode 100644
index 000000000..32c132289
--- /dev/null
+++ b/modules/mol/alg/tests/test_ost_dockq.py
@@ -0,0 +1,51 @@
+import unittest, os, sys
+import ost
+from ost import conop
+from ost import io, mol, seq, settings
+from ost.mol.alg import dockq
+import json
+
+def _LoadFile(file_name):
+ """Helper to avoid repeating input path over and over."""
+ return io.LoadPDB(os.path.join('testfiles', file_name))
+
+class TestDockQ(unittest.TestCase):
+
+ def test_dockq(self):
+
+ mdl = _LoadFile("lddtbs_mdl.pdb").Select("peptide=True")
+ trg = _LoadFile("lddtbs_ref_1r8q.1.pdb").Select("peptide=True")
+
+ dockq_result = dockq.DockQ(mdl, trg, "A", "B", "B", "A")
+
+ # compare to results computed with DockQ from https://github.com/bjornwallner/DockQ
+ # commit: 7a0a1c49ec70e2db68cb160abbe6aaf2f844a4ec
+ self.assertEqual(dockq_result["nnat"], 87)
+ self.assertEqual(dockq_result["nmdl"], 109)
+ self.assertAlmostEqual(dockq_result["fnat"], 0.828, places=3)
+ self.assertAlmostEqual(dockq_result["fnonnat"], 0.339, places=3)
+ self.assertAlmostEqual(dockq_result["irmsd"], 2.411, places=3)
+ self.assertAlmostEqual(dockq_result["lrmsd"], 6.568, places=3)
+ self.assertAlmostEqual(dockq_result["DockQ"], 0.578, places=3)
+
+ # enable "peptide mode" by passing -capri_peptide flag to DockQ executable
+ # not that we're dealing with a peptide here, but we can still check
+ # the slightly different parameterization...
+ dockq_result = dockq.DockQ(mdl, trg, "A", "B", "B", "A",
+ contact_dist_thresh = 4.0,
+ interface_dist_thresh = 8.0,
+ interface_cb = True)
+
+ self.assertEqual(dockq_result["nnat"], 54)
+ self.assertEqual(dockq_result["nmdl"], 76)
+ self.assertAlmostEqual(dockq_result["fnat"], 0.815, places=3)
+ self.assertAlmostEqual(dockq_result["fnonnat"], 0.421, places=3)
+ self.assertAlmostEqual(dockq_result["irmsd"], 1.579, places=3)
+ # for whatever reason, DockQ produces a slightly different number for
+ # lrmsd than above... Let's just slightly reduce accuracy
+ self.assertAlmostEqual(dockq_result["lrmsd"], 6.569, places=2)
+ self.assertAlmostEqual(dockq_result["DockQ"], 0.638, places=3)
+
+if __name__ == "__main__":
+ from ost import testutils
+ testutils.RunTests()
--
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