Merge branch 'main' into prody-signint

.github/workflows/main.yml

@@ -13,7 +13,7 @@ jobs:
     strategy:
       fail-fast: false
       matrix:
-        python-version: ["2.7", "3.8", "3.9", "3.10", "3.11", "3.12"]
+        python-version: ["2.7", "3.9", "3.10", "3.11", "3.12"]
 
     steps:
     - uses: actions/checkout@v2

prody/dynamics/__init__.py

@@ -119,6 +119,14 @@
 
   * :class:`.AdaptiveANM` - generate transitions between two conformers using best overlapping modes 
 
+ENM-MD hybrid methods
+===================
+
+The following classes and functions can be used to generate conformers using ENM-MD hybrid methods:
+
+  * :class:`.ClustENM` - generate conformers by exploring combinations of modes and clustering, using minimisation and optionally MD
+  * :function:`.ANMD` - generate conformers by traversing a number of individual modes, applying minimisation to each conformer
+
 Essential Site Scanning Analysis (ESSA)
 ========================================
 
@@ -367,3 +375,7 @@
 from . import logistic
 from .logistic import *
 __all__.extend(logistic.__all__)
+
+from . import anmd
+from .anmd import *
+__all__.extend(anmd.__all__)

prody/dynamics/anmd.py

@@ -0,0 +1,278 @@
+# -*- coding: utf-8 -*-
+'''
+Copyright (c) 2020-2022 Burak Kaynak, Pemra Doruker.
+
+Permission is hereby granted, free of charge, to any person obtaining a copy
+of this software and associated documentation files (the "Software"), to deal
+in the Software without restriction, including without limitation the rights
+to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
+copies of the Software, and to permit persons to whom the Software is
+furnished to do so, subject to the following conditions:
+
+The above copyright notice and this permission notice shall be included in all
+copies or substantial portions of the Software.
+
+THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
+IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
+FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
+AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
+LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
+OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
+SOFTWARE.
+'''
+
+__author__ = 'Anupam Banerjee'
+__credits__ = ['James Krieger']
+__email__ = ['[email protected]', '[email protected]']
+
+from numbers import Number
+import os
+
+from prody import LOGGER
+from prody.atomic.atomic import Atomic
+from prody.ensemble.ensemble import Ensemble
+from prody.proteins.pdbfile import parsePDB, writePDB
+
+from prody.dynamics.anm import ANM
+from prody.dynamics.clustenm import ClustENM
+from prody.dynamics.editing import extendModel
+from prody.dynamics.modeset import ModeSet
+from prody.dynamics.nma import NMA
+from prody.dynamics.sampling import traverseMode
+
+
+__all__ = ['runANMD']
+
+def runANMD(atoms, num_modes=2, max_rmsd=2., num_steps=2, tolerance=10.0,
+            **kwargs):
+    """Runs the ANMD hybrid simulation method ([CM22]_), which generates conformations
+    along single modes using :func:`.traverseModes` and minimises them. 
+    
+    The first non-zero mode is scaled to *max_rmsd*
+    and the remaining modes are scaled accordingly using their eigenvalues.
+
+    kwargs of traverseMode can be provided: pos, neg and reverse
+
+    :arg atoms: an object with atom and coordinate data.
+        This should be a complete atomic model. It is ok to be missing 
+        some side chain atoms and hydrogens, but not fragments, such as loops.
+    :type atoms: :class:`.Atomic`
+
+    :arg num_modes: number of modes to calculate
+        Default is 2
+    :type num_modes: int
+
+    :arg max_rmsd: maximum rmsd for non-zero mode 1
+        Default is 2.
+    :type max_rmsd: float
+
+    :arg num_steps: number of conformers in each direction for each mode
+        Default is 2
+    :type num_steps: int
+
+    :arg tolerance: tolerance for energy minimisation in OpenMM 
+        in kilojoule/mole/nanometer. Default is 10 as in OpenMM
+    :type tolerance: float
+
+    :arg skip_modes: number of modes to skip
+        Default is 0
+    :type skip_modes: int
+
+    :arg anm: your own NMA modes or ModeSet to use instead
+        Default is None
+    :type anm: :class:`.NMA`, :class:`.ANM`, :class:`.ModeSet`
+
+    .. [CM22] Mary Hongying Cheng, James M Krieger, Anupam Banerjee, Yufei Xiang, 
+            Burak Kaynak, Yi Shi, Moshe Arditi, Ivet Bahar. 
+            Impact of new variants on SARS-CoV-2 infectivity and neutralization: 
+            A molecular assessment of the alterations in the spike-host protein 
+            interactions. *iScience* **2022** 25(3):103939.
+    """
+    try:
+        from simtk.openmm.app import PDBFile, ForceField, \
+            Simulation, HBonds, NoCutoff
+        from simtk.openmm import LangevinIntegrator
+        from simtk.unit import nanometer, kelvin, picosecond, picoseconds, \
+            angstrom, kilojoule, mole
+    except ImportError:
+        raise ImportError('Please install PDBFixer and OpenMM to use ANMD')
+
+    if not isinstance(atoms, Atomic):
+        raise TypeError('atoms should be an Atomic object')
+
+    if not isinstance(num_modes, int):
+        raise TypeError('num_modes should be an integer')
+
+    if not isinstance(num_steps, int):
+        raise TypeError('num_steps should be an integer')
+
+    if not isinstance(max_rmsd, Number):
+        raise TypeError('max_rmsd should be a float')
+
+    if not isinstance(tolerance, Number):
+        raise TypeError('tolerance should be a float')
+    tolerance = tolerance * kilojoule/mole/nanometer
+
+    pos = kwargs.get('pos', True)
+    if not isinstance(pos, bool):
+        raise TypeError('pos should be a bool')
+
+    neg = kwargs.get('neg', True)
+    if not isinstance(neg, bool):
+        raise TypeError('neg should be a bool')
+
+    reverse = kwargs.get('reverse', False)
+    if not isinstance(reverse, bool):
+        raise TypeError('reverse should be a bool')
+
+    skip_modes = kwargs.get('skip_modes', 0)
+    if not isinstance(skip_modes, int):
+        raise TypeError('skip_modes should be an integer')
+
+    anm = kwargs.get('anm', None)
+    if not isinstance(anm, (type(None), NMA, ModeSet)):
+        raise TypeError('anm should be an NMA or ModeSet object')
+
+    pdb_name=atoms.getTitle().replace(' ', '_')
+
+    fix_name = pdb_name + '_fixed.pdb'
+    if os.path.exists(fix_name):
+        LOGGER.info('\nFixed structure found')
+    else:
+        clustenm=ClustENM()
+        clustenm.setAtoms(atoms)
+        clustenm.writePDBFixed()
+    pdb_fix = PDBFile(fix_name)
+
+    fixmin_name=pdb_name + '_fixedmin.pdb'
+    if os.path.exists(fixmin_name):
+        LOGGER.info('\nMinimised fixed structure found')
+    else:
+        LOGGER.info('\nMinimising fixed structure ...')
+        LOGGER.timeit('_anmd_min')
+
+        forcefield = ForceField("amber99sbildn.xml", "amber99_obc.xml")
+        system = forcefield.createSystem(pdb_fix.topology, 
+                                         nonbondedMethod=NoCutoff,
+                                         nonbondedCutoff=1*nanometer, 
+                                         constraints=HBonds)
+        integrator = LangevinIntegrator(300*kelvin, 1/picosecond, 
+                                        0.003*picoseconds)
+        simulation = Simulation(pdb_fix.topology, system, integrator)
+        simulation.context.setPositions(pdb_fix.positions)
+        simulation.minimizeEnergy(tolerance=tolerance)
+        positions = simulation.context.getState(getPositions=True).getPositions()
+        PDBFile.writeFile(simulation.topology, positions, open(fixmin_name, 'w'))
+        LOGGER.report('The fixed structure was minimised in %.2fs.\n',
+                        label='_anmd_min')
+
+    pdb_fixed=parsePDB(fixmin_name, compressed=False)
+
+    if skip_modes >= num_modes:
+        LOGGER.warn('skip_modes >= num_modes so no modes are used and minimised fixed structure is returned')
+        return pdb_fixed
+
+    calphas=pdb_fixed.select('calpha')
+    if anm is None:
+        anm=ANM()
+        anm.buildHessian(calphas)
+        anm.calcModes(n_modes=num_modes)
+    anm_ex, atoms_all = extendModel(anm, calphas, pdb_fixed)
+    anm_ex._indices = anm.getIndices()
+    eval_0=anm[0].getEigval()
+
+    ensembles = []
+    for i in range(skip_modes, num_modes):
+        modeNum = anm_ex.getIndices()[i]
+
+        eval_i=anm[i].getEigval()
+        sc_rmsd=((1/eval_i)**0.5/(1/eval_0)**0.5)*max_rmsd
+        traj_aa=traverseMode(anm_ex[i], atoms_all, n_steps=num_steps, rmsd=sc_rmsd,
+                             **kwargs)
+        traj_aa.setAtoms(atoms_all)
+
+        num_confs = traj_aa.numConfs()
+        LOGGER.info('\nMinimising {0} conformers for mode {1} ...'.format(num_confs, modeNum))
+
+        target_ensemble = Ensemble('mode {0} ensemble'.format(modeNum))
+        target_ensemble.setAtoms(atoms_all)
+        target_ensemble.setCoords(atoms_all)
+
+        for j, conf in enumerate(traj_aa):
+            jp1 = j+1
+            writePDB('temp1.pdb', conf)
+            pdb = PDBFile('temp1.pdb')
+            os.remove("temp1.pdb")
+
+            LOGGER.info('\nMinimising structure {0} along mode {1} ...'.format(jp1, modeNum))
+            LOGGER.timeit('_anmd_min')
+            forcefield = ForceField("amber99sbildn.xml", "amber99_obc.xml")
+            system = forcefield.createSystem(pdb.topology, 
+                                             nonbondedMethod=NoCutoff,
+                                             nonbondedCutoff=1*nanometer, 
+                                             constraints=HBonds)
+            integrator = LangevinIntegrator(300*kelvin, 1/picosecond, \
+                                            0.003*picoseconds)
+            simulation = Simulation(pdb.topology, system, integrator)
+            simulation.context.setPositions(pdb.positions)
+            simulation.minimizeEnergy(tolerance=tolerance)
+            positions = simulation.context.getState(getPositions=True).getPositions(
+                asNumpy=True).value_in_unit(angstrom)[:pdb.topology.getNumAtoms()]
+
+            target_ensemble.addCoordset(positions)
+
+            LOGGER.report('The structure was minimised in %.2fs.',
+                            label='_anmd_min')
+
+        ensembles.append(target_ensemble)
+
+    os.remove(fix_name)
+    os.remove(fixmin_name)
+
+    return ensembles
+
+
+if __name__=='__main__':
+    import sys
+    from prody.tests.datafiles import pathDatafile
+
+    pdb_filename = sys.argv[1] if len(sys.argv) > 1 else pathDatafile('1ubi')
+    num_modes = int(sys.argv[2]) if len(sys.argv) > 2 else 2
+    max_rmsd = float(sys.argv[3]) if len(sys.argv) > 3 else 2.
+    tol = float(sys.argv[4]) if len(sys.argv) > 4 else 10.
+
+    num_steps = int(sys.argv[5]) if len(sys.argv) > 5 else 2
+    skip_modes = int(sys.argv[6]) if len(sys.argv) > 6 else 0
+
+    pos = bool(sys.argv[7]) if len(sys.argv) > 7 else True
+    neg = bool(sys.argv[8]) if len(sys.argv) > 8 else True
+    reverse = bool(sys.argv[9]) if len(sys.argv) > 9 else False
+
+    anm_filename = sys.argv[10] if len(sys.argv) > 10 else None
+    anm = None
+    if anm_filename is not None:
+        if anm.endswith('nmd'):
+            anm, _ = parseNMD(anm_filename)
+        elif anm.endswith('npz'):
+            anm = loadModel(anm_filename)
+        else:
+            raise ValueError('anm should be an nmd or npz file or None')
+
+    pdb_name_ext = pdb_filename
+    if pdb_name_ext.endswith('.pdb'):
+        pdb_filename = pdb_name_ext[:-4]
+    else:
+        pdb_name_ext += '.pdb'
+
+    pdb = parsePDB(pdb_name_ext, compressed=False)
+
+    x = runANMD(pdb, num_modes=num_modes, max_rmsd=max_rmsd,
+                num_steps=num_steps, skip_modes=skip_modes, tolerance=tol,
+                pos=pos, neg=neg, reverse=reverse,
+                anm=anm)
+
+    pdb_basename = os.path.basename(pdb_filename)
+    for ens in x:
+        filename = pdb_basename + '_' + ens.getTitle().replace(' ', '_')
+        LOGGER.info('writing PDB file {0}'.format(filename))
+        writePDB(filename, ens)