Added GLYCAM (#3303)

* Added GLYCAM

* Improved tests and documentation

* Fixed incorrect external bonds

docs-source/usersguide/application/02_running_sims.rst

@@ -499,6 +499,7 @@ File                                 Parameters
 :file:`amber14/DNA.bsc1.xml`         DNA (alternative)
 :file:`amber14/RNA.OL3.xml`          RNA
 :file:`amber14/lipid17.xml`          Lipid
+:file:`amber14/GLYCAM_06j-1.xml`     Carbohydrates and glycosylated proteins\ :cite:`Kirschner2007`
 :file:`amber14/tip3p.xml`            TIP3P water model\ :cite:`Jorgensen1983` and ions
 :file:`amber14/tip3pfb.xml`          TIP3P-FB water model\ :cite:`Wang2014` and ions
 :file:`amber14/tip4pew.xml`          TIP4P-Ew water model\ :cite:`Horn2004` and ions
@@ -515,6 +516,18 @@ water model and ions\ :cite:`Wang2014`:
 
     forcefield = ForceField('amber14-all.xml', 'amber14/tip3pfb.xml')
 
+GLYCAM is not included by default, since it is quite large.  If your system contains
+carbohydrates, include that file as well:
+::
+
+    forcefield = ForceField('amber14-all.xml', 'amber14/tip3pfb.xml', 'amber14/GLYCAM_06j-1.xml')
+
+Be aware that GLYCAM works somewhat differently from most force fields.  It uses
+its own nonstandard `naming convention <http://legacy.glycam.org/docs/forcefield/glycam-naming-2/index.html>`_
+for carbohydrates, and requires your input file to follow it.  If any residues have
+names different from what it expects, GLYCAM will be unable to assign parameters
+to them.
+
 .. tip:: The solvent model XML files included under the :file:`amber14/` directory
          include both water *and* ions compatible with that water model, so if you
          mistakenly specify :file:`tip3p.xml` instead of :file:`amber14/tip3p.xml`,

docs-source/usersguide/application/03_model_building_editing.rst

@@ -67,6 +67,17 @@ If you want more control, it is possible to specify exactly which protonation
 state to use for particular residues.  For details, consult the API
 documentation for the Modeller class.
 
+By default, :class:`Modeller` loads information about hydrogens in standard
+amino acids and nucleic acids.  You can call :meth:`loadHydrogenDefinitions` to
+load definitions for other types of molecules.  In particular, if your system
+contains carbohydrates that you plan to simulate with the GLYCAM force field, call
+::
+
+    Modeller.loadHydrogenDefinitions('glycam-hydrogens.xml')
+
+All subsequent calls to :meth:`addHydrogens` will make use of the newly loaded
+definitions.
+
 Adding Solvent
 **************
 

docs-source/usersguide/references.bib

@@ -207,6 +207,17 @@
    type = {Journal Article}
 }
 
+@article{Kirschner2007
+   author = {Kirschner, Karl N. and Yongye, Austin B. and Tschampel, Sarah M. and González-Outeiriño, Jorge and Daniels, Charlisa R and Foley, B. Lachele and Woods, Robert J.},
+   title = {GLYCAM06: A generalizable biomolecular force field. Carbohydrates},
+   journal = {Journal of Computational Chemistry},
+   volume = {29},
+   issue = {4},
+   pages = {622-655},
+   year = {2007},
+   type = {Journal Article}
+}
+
 @inbook{Kollman1997
    author = {Kollman, P.A. and Dixon, R. and Cornell, W. and Fox, T. and Chipot, C. and Pohorille, A.},
    title = {Computer Simulation of Biomolecular Systems},

wrappers/python/openmm/app/forcefield.py

@@ -492,9 +492,13 @@ class ForceField(object):
 
         A template matcher is a callable object that can be invoked as::
         
-            template = f(forcefield, residue)
+            template = f(forcefield, residue, bondedToAtom, ignoreExternalBonds, ignoreExtraParticles)
         
-        where ``forcefield`` is the ForceField invoking it and ``residue`` is a openmm.app.Residue object.
+        where ``forcefield`` is the ForceField invoking it, ``residue`` is an openmm.app.Residue object,
+        ``bondedToAtom[i]`` is the set of atoms bonded to atom index i, and ``ignoreExternalBonds`` and
+        ``ignoreExtraParticles`` indicate whether external bonds and extra particules should be considered
+        in matching templates.
+
         It should return a _TemplateData object that matches the residue.  Alternatively it may return
         None, in which case the standard logic will be used to find a template for the residue.
 
@@ -981,11 +985,11 @@ class ForceField(object):
         template = None
         matches = None
         for matcher in self._templateMatchers:
-            template = matcher(self, res)
+            template = matcher(self, res, bondedToAtom, ignoreExternalBonds, ignoreExtraParticles)
             if template is not None:
                 match = compiled.matchResidueToTemplate(res, template, bondedToAtom, ignoreExternalBonds, ignoreExtraParticles)
                 if match is None:
-                    raise ValueError('A custom template matcher returned a template for residue %s, but it does not match the residue.' % res.name)
+                    raise ValueError('A custom template matcher returned a template for residue %d (%s), but it does not match the residue.' % (res.index, res.name))
                 return [template, match]
         if templateSignatures is None:
             templateSignatures = self._templateSignatures

wrappers/python/openmm/app/modeller.py

@@ -35,7 +35,7 @@ __author__ = "Peter Eastman"
 __version__ = "1.0"
 
 from openmm.app import Topology, PDBFile, ForceField
-from openmm.app.forcefield import AllBonds, CutoffNonPeriodic, CutoffPeriodic, DrudeGenerator
+from openmm.app.forcefield import AllBonds, CutoffNonPeriodic, CutoffPeriodic, DrudeGenerator, _getDataDirectories
 from openmm.app.internal import compiled
 from openmm.vec3 import Vec3
 from openmm import System, Context, NonbondedForce, CustomNonbondedForce, HarmonicBondForce, HarmonicAngleForce, VerletIntegrator, LangevinIntegrator, LocalEnergyMinimizer
@@ -653,8 +653,28 @@ class Modeller(object):
         The built in hydrogens.xml file containing definitions for standard amino acids and nucleotides is loaded automatically.
         This method can be used to load additional definitions for other residue types.  They will then be used in subsequent
         calls to addHydrogens().
+
+        Parameters
+        ----------
+        file : string or file
+            An XML file containing hydrogen definitions.  It may be either an
+            absolute file path, a path relative to the current working
+            directory, a path relative to this module's data subdirectory (for
+            built in sets of definitions), or an open file-like object with a read()
+            method from which the data can be loaded.
         """
-        tree = etree.parse(file)
+        tree = None
+        try:
+            # this handles either filenames or open file-like objects
+            tree = etree.parse(file)
+        except IOError:
+            for dataDir in _getDataDirectories():
+                f = os.path.join(dataDir, file)
+                if os.path.isfile(f):
+                    tree = etree.parse(f)
+                    break
+        if tree is None:
+            raise ValueError('Could not locate file')
         infinity = float('Inf')
         for residue in tree.getroot().findall('Residue'):
             resName = residue.attrib['name']
@@ -869,7 +889,8 @@ class Modeller(object):
                     parents = [atom for atom in residue.atoms() if atom.element != elem.hydrogen]
                     parentNames = [atom.name for atom in parents]
                     hydrogens = [h for h in spec.hydrogens if (variant is None and pH <= h.maxph) or (h.variants is None and pH <= h.maxph) or (h.variants is not None and variant in h.variants)]
-                    hydrogens = [h for h in hydrogens if h.terminal is None or (isNTerminal and h.terminal == 'N') or (isCTerminal and h.terminal == 'C')]
+                    hydrogens = [h for h in hydrogens if h.terminal is None or (isNTerminal and 'N' in h.terminal) or (isCTerminal and 'C' in h.terminal) or
+                                 ((not isNTerminal) and (not isCTerminal) and '-' in h.terminal)]
                     hydrogens = [h for h in hydrogens if h.parent in parentNames]
 
                     # Loop over atoms in the residue, adding them to the new topology along with required hydrogens.

wrappers/python/tests/TestForceField.py

@@ -466,7 +466,7 @@ class TestForceField(unittest.TestCase):
         self.assertRaises(Exception, lambda: ff.createSystem(top))
         
         # Register a template matcher that selects a particular one.
-        def matcher(ff, res):
+        def matcher(ff, res, bondedToAtom, ignoreExternalBonds, ignoreExtraParticles):
             return ff._templates['HOH2']
         ff.registerTemplateMatcher(matcher)
         
@@ -1193,7 +1193,29 @@ self.scriptExecuted = True
 """
         ff = ForceField(StringIO(xml))
         self.assertTrue(ff.scriptExecuted)
-        
+
+    def test_Glycam(self):
+        """Test computing energy with GLYCAM."""
+        ff = ForceField('amber14/protein.ff14SB.xml', 'amber14/GLYCAM_06j-1.xml')
+        pdb = PDBFile('systems/glycopeptide.pdb')
+        system = ff.createSystem(pdb.topology)
+        for i, f in enumerate(system.getForces()):
+            f.setForceGroup(i)
+        integrator = VerletIntegrator(0.001)
+        context = Context(system, integrator, Platform.getPlatformByName('Reference'))
+        context.setPositions(pdb.positions)
+        energies = {}
+        for i, f in enumerate(system.getForces()):
+            energy = context.getState(getEnergy=True, groups={i}).getPotentialEnergy().value_in_unit(kilojoules_per_mole)
+            energies[f.getName()] = energy
+
+        # Compare to values computed with ParmEd.
+
+        self.assertAlmostEqual(32.14082401103625, energies['HarmonicBondForce'], 4)
+        self.assertAlmostEqual(48.92017455984504, energies['HarmonicAngleForce'], 3)
+        self.assertAlmostEqual(291.61241586209286, energies['PeriodicTorsionForce'], 4)
+        self.assertAlmostEqual(1547.011267801862, energies['NonbondedForce'], 4)
+        self.assertAlmostEqual(1919.6846822348361, sum(list(energies.values())), 3)
 
 class AmoebaTestForceField(unittest.TestCase):
     """Test the ForceField.createSystem() method with the AMOEBA forcefield."""

wrappers/python/tests/TestModeller.py

@@ -952,6 +952,20 @@ class TestModeller(unittest.TestCase):
 
         validate_equivalence(self, topology_LYN, topology_after)
 
+    def test_addHydrogensGlycam(self):
+        """Test adding hydrogens for GLYCAM."""
+        pdb = PDBFile('systems/glycopeptide.pdb')
+        Modeller.loadHydrogenDefinitions('glycam-hydrogens.xml')
+        modeller = Modeller(pdb.topology, pdb.positions)
+        hydrogens = [a for a in modeller.topology.atoms() if a.element == element.hydrogen]
+        modeller.delete(hydrogens)
+        self.assertTrue(modeller.topology.getNumAtoms() < pdb.topology.getNumAtoms())
+        modeller.addHydrogens()
+        self.assertEqual(modeller.topology.getNumAtoms(), pdb.topology.getNumAtoms())
+        for res1, res2 in zip(pdb.topology.residues(), modeller.topology.residues()):
+            names1 = sorted([a.name for a in res1.atoms()])
+            names2 = sorted([a.name for a in res2.atoms()])
+            self.assertEqual(names1, names2)
 
     def test_removeExtraHydrogens(self):
         """Test that addHydrogens() can remove hydrogens that shouldn't be there. """

wrappers/python/tests/systems/glycopeptide.pdb

+HETATM    1  N   NLN A   1      -4.410  -2.879   8.958  1.00  0.00           N  
+HETATM    2  CA  NLN A   1      -3.080  -3.453   8.940  1.00  0.00           C  
+HETATM    3  C   NLN A   1      -2.993  -4.600   7.943  1.00  0.00           C  
+HETATM    4  O   NLN A   1      -3.241  -5.752   8.293  1.00  0.00           O  
+HETATM    5  CB  NLN A   1      -2.698  -3.999  10.312  1.00  0.00           C  
+HETATM    6  CG  NLN A   1      -1.301  -4.603  10.292  1.00  0.00           C  
+HETATM    7  ND2 NLN A   1      -0.855  -5.115  11.441  1.00  0.00           N  
+HETATM    8  OD1 NLN A   1      -0.638  -4.606   9.257  1.00  0.00           O  
+HETATM    9  HA  NLN A   1      -2.357  -2.689   8.655  1.00  0.00           H  
+HETATM   10  HB2 NLN A   1      -2.718  -3.191  11.043  1.00  0.00           H  
+HETATM   11  HB3 NLN A   1      -3.407  -4.772  10.606  1.00  0.00           H  
+HETATM   12 HD21 NLN A   1      -1.440  -5.086  12.264  1.00  0.00           H  
+HETATM   13  H1  NLN A   1      -4.979  -3.382   8.293  1.00  0.00           H  
+HETATM   14  H2  NLN A   1      -4.295  -1.929   8.634  1.00  0.00           H  
+HETATM   15  H3  NLN A   1      -4.764  -3.055   9.888  1.00  0.00           H  
+ATOM     16  N   ALA A   2      -2.638  -4.282   6.695  1.00  0.00           N  
+ATOM     17  CA  ALA A   2      -2.520  -5.283   5.654  1.00  0.00           C  
+ATOM     18  C   ALA A   2      -2.103  -4.653   4.333  1.00  0.00           C  
+ATOM     19  O   ALA A   2      -2.951  -4.252   3.539  1.00  0.00           O  
+ATOM     20  CB  ALA A   2      -3.846  -6.002   5.430  1.00  0.00           C  
+ATOM     21  H   ALA A   2      -2.444  -3.321   6.455  1.00  0.00           H  
+ATOM     22  HA  ALA A   2      -1.769  -6.019   5.941  1.00  0.00           H  
+ATOM     23  HB1 ALA A   2      -4.606  -5.279   5.134  1.00  0.00           H  
+ATOM     24  HB2 ALA A   2      -3.727  -6.747   4.644  1.00  0.00           H  
+ATOM     25  HB3 ALA A   2      -4.153  -6.494   6.353  1.00  0.00           H  
+HETATM   26  N   NLN A   3      -0.792  -4.566   4.099  1.00  0.00           N  
+HETATM   27  CA  NLN A   3      -0.269  -3.986   2.879  1.00  0.00           C  
+HETATM   28  C   NLN A   3       1.253  -4.011   2.869  1.00  0.00           C  
+HETATM   29  O   NLN A   3       1.896  -3.068   3.325  1.00  0.00           O  
+HETATM   30  CB  NLN A   3      -0.712  -2.535   2.726  1.00  0.00           C  
+HETATM   31  CG  NLN A   3      -0.162  -1.926   1.444  1.00  0.00           C  
+HETATM   32  ND2 NLN A   3      -0.484  -0.653   1.201  1.00  0.00           N  
+HETATM   33  OD1 NLN A   3       0.541  -2.593   0.688  1.00  0.00           O  
+HETATM   34  H   NLN A   3      -0.133  -4.909   4.783  1.00  0.00           H  
+HETATM   35  HA  NLN A   3      -0.632  -4.553   2.022  1.00  0.00           H  
+HETATM   36  HB2 NLN A   3      -1.800  -2.488   2.695  1.00  0.00           H  
+HETATM   37  HB3 NLN A   3      -0.347  -1.952   3.572  1.00  0.00           H  
+HETATM   38 HD21 NLN A   3      -1.065  -0.149   1.855  1.00  0.00           H  
+ATOM     39  N   ALA A   4       1.829  -5.096   2.345  1.00  0.00           N  
+ATOM     40  CA  ALA A   4       3.270  -5.240   2.277  1.00  0.00           C  
+ATOM     41  C   ALA A   4       3.658  -6.566   1.637  1.00  0.00           C  
+ATOM     42  O   ALA A   4       3.815  -7.570   2.329  1.00  0.00           O  
+ATOM     43  CB  ALA A   4       3.892  -5.195   3.669  1.00  0.00           C  
+ATOM     44  H   ALA A   4       1.258  -5.846   1.982  1.00  0.00           H  
+ATOM     45  HA  ALA A   4       3.689  -4.430   1.682  1.00  0.00           H  
+ATOM     46  HB1 ALA A   4       3.489  -6.006   4.275  1.00  0.00           H  
+ATOM     47  HB2 ALA A   4       4.973  -5.306   3.588  1.00  0.00           H  
+ATOM     48  HB3 ALA A   4       3.660  -4.240   4.140  1.00  0.00           H  
+HETATM   49  N   NLN A   5       3.812  -6.567   0.311  1.00  0.00           N  
+HETATM   50  CA  NLN A   5       4.180  -7.765  -0.416  1.00  0.00           C  
+HETATM   51  C   NLN A   5       4.288  -7.488  -1.909  1.00  0.00           C  
+HETATM   52  O   NLN A   5       4.072  -6.362  -2.352  1.00  0.00           O  
+HETATM   53  CB  NLN A   5       3.144  -8.866  -0.219  1.00  0.00           C  
+HETATM   54  CG  NLN A   5       3.531 -10.125  -0.983  1.00  0.00           C  
+HETATM   55  ND2 NLN A   5       2.696 -11.162  -0.887  1.00  0.00           N  
+HETATM   56  OD1 NLN A   5       4.564 -10.158  -1.648  1.00  0.00           O  
+HETATM   57  OXT NLN A   5       4.591  -8.387  -2.689  1.00  0.00           O  
+HETATM   58  H   NLN A   5       3.671  -5.716  -0.214  1.00  0.00           H  
+HETATM   59  HA  NLN A   5       5.144  -8.126  -0.058  1.00  0.00           H  
+HETATM   60  HB2 NLN A   5       3.069  -9.111   0.840  1.00  0.00           H  
+HETATM   61  HB3 NLN A   5       2.175  -8.523  -0.581  1.00  0.00           H  
+HETATM   62 HD21 NLN A   5       1.859 -11.083  -0.328  1.00  0.00           H  
+TER      63      NLN A   5
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+HETATM  111  C3  0GB B   3       4.580 -14.386  -1.656  1.00  0.00           C  
+HETATM  112  O3  0GB B   3       5.765 -14.961  -1.041  1.00  0.00           O  
+HETATM  113  C4  0GB B   3       3.375 -15.320  -1.390  1.00  0.00           C  
+HETATM  114  O4  0GB B   3       3.592 -16.579  -2.071  1.00  0.00           O  
+HETATM  115  C5  0GB B   3       2.102 -14.719  -1.865  1.00  0.00           C  
+HETATM  116  O5  0GB B   3       1.913 -13.348  -1.299  1.00  0.00           O  
+HETATM  117  C6  0GB B   3       0.877 -15.586  -1.516  1.00  0.00           C  
+HETATM  118  O6  0GB B   3      -0.321 -14.965  -2.019  1.00  0.00           O  
+HETATM  119  H1  0GB B   3       3.052 -12.206  -2.657  1.00  0.00           H  
+HETATM  120  H2  0GB B   3       4.347 -13.008   0.002  1.00  0.00           H  
+HETATM  121  H3  0GB B   3       4.747 -14.316  -2.733  1.00  0.00           H  
+HETATM  122  H4  0GB B   3       3.294 -15.511  -0.318  1.00  0.00           H  
+HETATM  123  H5  0GB B   3       2.170 -14.634  -2.951  1.00  0.00           H  
+HETATM  124  H2O 0GB B   3       5.252 -11.205  -1.219  1.00  0.00           H  
+HETATM  125  H3O 0GB B   3       6.485 -14.325  -1.150  1.00  0.00           H  
+HETATM  126  H61 0GB B   3       0.971 -16.578  -1.957  1.00  0.00           H  
+HETATM  127  H62 0GB B   3       0.790 -15.698  -0.434  1.00  0.00           H  
+HETATM  128  H4O 0GB B   3       4.480 -16.885  -1.839  1.00  0.00           H  
+HETATM  129  H6O 0GB B   3      -0.349 -14.059  -1.695  1.00  0.00           H  
+TER     130      0GB B   3
+CONECT    1    2   13   14   15
+CONECT    2    1    3    5    9
+CONECT    3   16    2    4
+CONECT    4    3
+CONECT    5    2    6   10   11
+CONECT    6    5    7    8
+CONECT    7    6   12   64
+CONECT    8    6
+CONECT    9    2
+CONECT   10    5
+CONECT   11    5
+CONECT   12    7
+CONECT   13    1
+CONECT   14    1
+CONECT   15    1
+CONECT   16    3
+CONECT   18   26
+CONECT   26   18   27   34
+CONECT   27   26   28   30   35
+CONECT   28   39   27   29
+CONECT   29   28
+CONECT   30   27   31   36   37
+CONECT   31   30   32   33
+CONECT   32   31   38   86
+CONECT   33   31
+CONECT   34   26
+CONECT   35   27
+CONECT   36   30
+CONECT   37   30
+CONECT   38   32
+CONECT   39   28
+CONECT   41   49
+CONECT   49   41   50   58
+CONECT   50   49   51   53   59
+CONECT   51   50   52   57
+CONECT   52   51
+CONECT   53   50   54   60   61
+CONECT   54   53   55   56
+CONECT   55   54   62  108
+CONECT   56   54
+CONECT   57   51
+CONECT   58   49
+CONECT   59   50
+CONECT   60   53
+CONECT   61   53
+CONECT   62   55
+CONECT   64    7   65   72   75
+CONECT   65   64   66   76   67
+CONECT   66   65   80
+CONECT   67   65   68   77   69
+CONECT   68   67   81
+CONECT   69   67   70   78   71
+CONECT   70   69   84
+CONECT   71   69   73   79   72
+CONECT   72   64   71
+CONECT   73   71   74   82   83
+CONECT   74   73   85
+CONECT   75   64
+CONECT   76   65
+CONECT   77   67
+CONECT   78   69
+CONECT   79   71
+CONECT   80   66
+CONECT   81   68
+CONECT   82   73
+CONECT   83   73
+CONECT   84   70
+CONECT   85   74
+CONECT   86   32   87   94   97
+CONECT   87   86   88   98   89
+CONECT   88   87  102
+CONECT   89   87   90   99   91
+CONECT   90   89  103
+CONECT   91   89   92  100   93
+CONECT   92   91  106
+CONECT   93   91   95  101   94
+CONECT   94   86   93
+CONECT   95   93   96  104  105
+CONECT   96   95  107
+CONECT   97   86
+CONECT   98   87
+CONECT   99   89
+CONECT  100   91
+CONECT  101   93
+CONECT  102   88
+CONECT  103   90
+CONECT  104   95
+CONECT  105   95
+CONECT  106   92
+CONECT  107   96
+CONECT  108   55  109  116  119
+CONECT  109  108  110  120  111
+CONECT  110  109  124
+CONECT  111  109  112  121  113
+CONECT  112  111  125
+CONECT  113  111  114  122  115
+CONECT  114  113  128
+CONECT  115  113  117  123  116
+CONECT  116  108  115
+CONECT  117  115  118  126  127
+CONECT  118  117  129
+CONECT  119  108
+CONECT  120  109
+CONECT  121  111
+CONECT  122  113
+CONECT  123  115
+CONECT  124  110
+CONECT  125  112
+CONECT  126  117
+CONECT  127  117
+CONECT  128  114
+CONECT  129  118
+END