diff --git a/sidechain/doc/index.rst b/sidechain/doc/index.rst
index 7024172270d20bf4cec1ccdabded5110ac8226d7..1c11cb815a948b0886af2b9300556c60302fb71e 100644
--- a/sidechain/doc/index.rst
+++ b/sidechain/doc/index.rst
@@ -33,7 +33,7 @@ The simplest usage of the module is provided by the :func:`Reconstruct` function
.. method:: Reconstruct(prot, keep_sidechains=False, build_disulfids, \
rotamer_model="frm", consider_hbonds=True, \
- rotamer_library=None, add_polar_hydrogens=False)
+ rotamer_library=None)
The function takes a structure and reconstructs its sidechains given the input
parameters.
@@ -61,10 +61,6 @@ The simplest usage of the module is provided by the :func:`Reconstruct` function
:param rotamer_library: A rotamer library to extract the
rotamers from.
- :param add_polar_hydrogens: All polar hydrogens will be constructed if
- **consider_hbonds** is True.
- If this flag is activated, they'll be added to the
- structure.
:type prot: :class:`ost.mol.EntityHandle`
:type keep_sidechains: :class:`bool`
@@ -72,7 +68,6 @@ The simplest usage of the module is provided by the :func:`Reconstruct` function
:type rotamer_model: :class:`str`
:type consider_hbonds: :class:`bool`
:type rotamer_library: :class:`BBDepRotamerLib` / :class:`RotamerLib`
- :type add_polar_hydrogens: :class:`bool`
Sidechain Module Functionality
diff --git a/sidechain/pymod/_reconstruct_sidechains.py b/sidechain/pymod/_reconstruct_sidechains.py
index fabd97e5c0cf37109d824fe7158d62b192b843ad..2fc82977addb81ed388ae3f15076bb286cab26e5 100644
--- a/sidechain/pymod/_reconstruct_sidechains.py
+++ b/sidechain/pymod/_reconstruct_sidechains.py
@@ -1,34 +1,10 @@
from . import _sidechain as sidechain
from ost import geom
+from ost import mol
def Reconstruct(ent, keep_sidechains = False, build_disulfids = True,
rotamer_model = "frm", consider_hbonds = True,
- rotamer_library = None, add_polar_hydrogens=False):
-
- name_id_mapper = dict()
- name_id_mapper["ARG"] = sidechain.ARG
- name_id_mapper["ASN"] = sidechain.ASN
- name_id_mapper["ASP"] = sidechain.ASP
- name_id_mapper["GLN"] = sidechain.GLN
- name_id_mapper["GLU"] = sidechain.GLU
- name_id_mapper["LYS"] = sidechain.LYS
- name_id_mapper["SER"] = sidechain.SER
- name_id_mapper["CYS"] = sidechain.CYS
- name_id_mapper["MET"] = sidechain.MET
- name_id_mapper["TRP"] = sidechain.TRP
- name_id_mapper["TYR"] = sidechain.TYR
- name_id_mapper["THR"] = sidechain.THR
- name_id_mapper["VAL"] = sidechain.VAL
- name_id_mapper["ILE"] = sidechain.ILE
- name_id_mapper["LEU"] = sidechain.LEU
- name_id_mapper["PRO"] = sidechain.PRO
- name_id_mapper["HSD"] = sidechain.HSD
- name_id_mapper["HSE"] = sidechain.HSE
- name_id_mapper["HIS"] = sidechain.HIS
- name_id_mapper["PHE"] = sidechain.PHE
- name_id_mapper["ALA"] = sidechain.ALA
- name_id_mapper["GLY"] = sidechain.GLY
- name_id_mapper["MSE"] = sidechain.MET
+ rotamer_library = None):
if rotamer_model.lower() == "frm":
use_frm = True
@@ -50,23 +26,53 @@ def Reconstruct(ent, keep_sidechains = False, build_disulfids = True,
prot = ent.Select("peptide=true")
incomplete_sidechains = list()
+ #extract rotamer ids
+ rotamer_ids = [sidechain.ALA] * len(prot.residues)
+ for i,r in enumerate(prot.residues):
+ rot_id = sidechain.TLCToRotID(r.GetName())
+ if rot_id == sidechain.XXX:
+ continue # no idea what it is, so we stick with ALA
+ # => don't model sidechain
+ rotamer_ids[i] = rot_id
#extract dihedral angles
phi_angles = [0.0] * len(prot.residues)
psi_angles = [0.0] * len(prot.residues)
for i,r in enumerate(prot.residues):
+
phi = -1.0472
psi = -0.7854
tor = r.GetPhiTorsion()
if tor.IsValid():
phi = tor.GetAngle()
+ elif i > 0:
+ r_prev = prot.residues[i-1]
+ if mol.InSequence(r_prev.handle,r.handle):
+ c_prev = r_prev.FindAtom("C")
+ n = r.FindAtom("N")
+ ca = r.FindAtom("CA")
+ c = r.FindAtom("C")
+ if c_prev.IsValid() and n.IsValid() and ca.IsValid() and c.IsValid():
+ phi = geom.DihedralAngle(c_prev.GetPos(),n.GetPos(),
+ ca.GetPos(),c.GetPos())
tor = r.GetPsiTorsion()
if tor.IsValid():
psi = tor.GetAngle()
-
+ elif i < (len(prot.residues) - 1):
+ r_next = prot.residues[i+1]
+ if mol.InSequence(r.handle,r_next.handle):
+ n = r.FindAtom("N")
+ ca = r.FindAtom("CA")
+ c = r.FindAtom("C")
+ n_next = r_next.FindAtom("N")
+ if n.IsValid() and ca.IsValid() and c.IsValid() and n_next.IsValid():
+ psi = geom.DihedralAngle(n.GetPos(), ca.GetPos(),
+ c.GetPos(), n_next.GetPos())
+
+
phi_angles[i] = phi
psi_angles[i] = psi
@@ -83,11 +89,8 @@ def Reconstruct(ent, keep_sidechains = False, build_disulfids = True,
#build up backbone frame
for i,r in enumerate(prot.residues):
try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- rot_id = sidechain.ALA
- try:
- frame_residue = sidechain.ConstructBackboneFrameResidue(r.GetHandle(),rot_id,
+ frame_residue = sidechain.ConstructBackboneFrameResidue(r.handle,
+ rotamer_ids[i],
i,rotamer_settings,
phi_angles[i],
r.HasProp("n_ter"),
@@ -96,209 +99,194 @@ def Reconstruct(ent, keep_sidechains = False, build_disulfids = True,
except:
continue
- if keep_sidechains:
- for i,r in enumerate(prot.residues):
- try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- continue
- if rot_id == sidechain.CYS:
- continue #cysteins will be handled seperately
- if rot_id == sidechain.ALA or rot_id == sidechain.GLY:
- continue
- try:
- frame_residue = sidechain.ConstructSidechainFrameResidue(r.GetHandle(),rot_id,
- i,rotamer_settings)
- frame_residues.append(frame_residue)
- except:
- incomplete_sidechains.append(i)
- else:
- for i,r in enumerate(prot.residues):
- try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- continue
- if rot_id not in [sidechain.GLY, sidechain.ALA]:
- incomplete_sidechains.append(i)
+ frame = None
- #look for cysteins and evaluate potential disulfid bonds
- final_disulfid_indices = list()
if build_disulfids:
- cystein_info = list()
- for i,r in enumerate(prot.residues):
- try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- continue
- if rot_id == sidechain.CYS:
- ca = r.FindAtom("CA")
- cb = r.FindAtom("CB")
- if ca.IsValid() and cb.IsValid():
- cystein_info.append((ca.GetPos(),cb.GetPos(),i))
+ cystein_indices = list()
+
+ if keep_sidechains:
+ #let's add all complete sidechains except the cysteins to the frame
+ for i,r in enumerate(prot.residues):
+
+ if rotamer_ids[i] == sidechain.CYS:
+ cystein_indices.append(i)
+ continue
+
+ if rotamer_ids[i] == sidechain.ALA or rotamer_ids[i] == sidechain.GLY:
+ continue #no sidechain to model
+
+ try:
+ frame_residue = sidechain.ConstructSidechainFrameResidue(r.handle,
+ rotamer_ids[i],
+ i,rotamer_settings)
+ frame_residues.append(frame_residue)
+ except:
+ incomplete_sidechains.append(i)
+ else:
+ #let's add everything except cysteins to the incomplete sidechains
+ for i,r in enumerate(prot.residues):
+
+ if rotamer_ids[i] == sidechain.CYS:
+ cystein_indices.append(i)
+ continue
+
+ if rotamer_ids[i] == sidechain.ALA or rotamer_ids[i] == sidechain.GLY:
+ continue #no sidechain to model
+
+ incomplete_sidechains.append(i)
+ #let's generate the frame without any cystein sidechains
+ #this is required for the disulfid score evaluation
frame = sidechain.Frame(frame_residues)
- for i in range(len(cystein_info)):
+ #some info we have to keep track of when evaluating disulfid bonds
+ cystein_rotamers = list()
+ disulfid_indices = list()
+ cys_ca_positions = list()
+ cys_cb_positions = list()
+
+ for i in cystein_indices:
+
+ rot_grop = None
+ r = prot.residues[i]
+ ca = r.FindAtom("CA")
+ cb = r.FindAtom("CB")
- if cystein_info[i][2] in final_disulfid_indices:
+ if not (ca.IsValid() and cb.IsValid()):
continue
- complete_i = keep_sidechains and prot.residues[cystein_info[i][2]].FindAtom("SG").IsValid()
- i_ca_pos = cystein_info[i][0]
- i_cb_pos = cystein_info[i][1]
- i_index = cystein_info[i][2]
+ cys_ca_positions.append(ca.GetPos())
+ cys_cb_positions.append(cb.GetPos())
+
+ if use_frm:
+ if bbdep:
+ rot_group = sidechain.ConstructFRMRotamerGroup(r.handle,
+ sidechain.CYD,i,
+ rotamer_library,
+ rotamer_settings,
+ phi_angles[i],
+ psi_angles[i])
+ else:
+ rot_group = sidechain.ConstructFRMRotamerGroup(r.handle,
+ sidechain.CYD,i,
+ rotamer_library,
+ rotamer_settings)
+ else:
+ if bbdep:
+ rot_group = sidechain.ConstructRRMRotamerGroup(r.handle,
+ sidechain.CYD,i,
+ rotamer_library,
+ rotamer_settings,
+ phi_angles[i],
+ psi_angles[i])
+ else:
+ rot_group = sidechain.ConstructRRMRotamerGroup(r.handle,
+ sidechain.CYD,i,
+ rotamer_library,
+ rotamer_settings)
+
+ frame.AddFrameEnergy(rot_group)
+ cystein_rotamers.append(rot_group)
+
+ for i in range(len(cystein_rotamers)):
+ for j in range(i+1, len(cystein_rotamers)):
+
+ if geom.Distance(cys_ca_positions[i], cys_ca_positions[j]) > 8.0:
+ continue #they're too far for a disulfid bond
+
+ if cystein_indices[i] in disulfid_indices or cystein_indices[j] in disulfid_indices:
+ continue #one of them already participates in a disulfid bond!
+ #that one might be bether but right now is first come
+ #first served principle
+
+ min_score = float("inf")
+ min_index_k = -1
+ min_index_l = -1
+
+ for k in range(len(cystein_rotamers[i])):
+ for l in range(len(cystein_rotamers[j])):
+ score = sidechain.DisulfidScore(cystein_rotamers[i][k],
+ cystein_rotamers[j][l],
+ cys_ca_positions[i],
+ cys_cb_positions[i],
+ cys_ca_positions[j],
+ cys_cb_positions[j])
+ if score < min_score:
+ min_index_k = k
+ min_index_l = l
+ min_score = score
+
+ if min_score < 45.0:
+ disulfid_indices.append(cystein_indices[i])
+ disulfid_indices.append(cystein_indices[j])
+ particle_list = list()
+ particle_list.append(cystein_rotamers[i][min_index_k][0])
+ new_frame_residue_i = sidechain.FrameResidue(particle_list,cystein_indices[i])
+ particle_list = list()
+ particle_list.append(cystein_rotamers[j][min_index_l][0])
+ new_frame_residue_j = sidechain.FrameResidue(particle_list,cystein_indices[j])
+ frame_residues.append(new_frame_residue_i)
+ frame_residues.append(new_frame_residue_j)
+ #set the position in the proteins residues
+ cystein_rotamers[i][min_index_k].ApplyOnResidue(prot.residues[cystein_indices[i]].handle,
+ consider_hydrogens=False)
+ cystein_rotamers[j][min_index_l].ApplyOnResidue(prot.residues[cystein_indices[j]].handle,
+ consider_hydrogens=False)
+
+ #All cysteins participating in a disulfid bond have been applied to the
+ #structure and added to the frame.
+ #All remaining ones have to be handled according the given flags.
+ for idx in cystein_indices:
+ if idx in disulfid_indices:
+ continue #it's all fine
+ if keep_sidechains:
+ try:
+ frame_residue = sidechain.ConstructSidechainFrameResidue(prot.residues[idx].handle,
+ rotamer_ids[idx],
+ idx,rotamer_settings)
+ frame_residues.append(frame_residue)
+ except:
+ incomplete_sidechains.append(idx)
+ else:
+ incomplete_sidechains.append(idx)
+
+ #we finally have to rebuild the frame if any disulfid bonds have been built
+ if len(disulfid_indices) > 0:
+ frame = sidechain.Frame(frame_residues)
- for j in range(i+1,len(cystein_info)):
- if cystein_info[j][2] in final_disulfid_indices:
- continue
-
- complete_j = keep_sidechains and prot.residues[cystein_info[j][2]].FindAtom("SG").IsValid()
-
- if complete_i and complete_j:
- continue #they're already there
-
- if geom.Distance(i_ca_pos,cystein_info[j][0]) < 8:
- j_ca_pos = cystein_info[j][0]
- j_cb_pos = cystein_info[j][1]
- j_index = cystein_info[j][2]
-
-
- if use_frm:
- if bbdep:
- rot_group_one = sidechain.ConstructFRMRotamerGroup(prot.residues[cystein_info[i][2]].GetHandle(),
- sidechain.CYD,cystein_info[i][2],
- rotamer_library,rotamer_settings,
- phi_angles[i_index],psi_angles[i_index])
-
- rot_group_two = sidechain.ConstructFRMRotamerGroup(prot.residues[cystein_info[j][2]].GetHandle(),
- sidechain.CYD,cystein_info[j][2],
- rotamer_library,rotamer_settings,
- phi_angles[j_index],psi_angles[j_index])
- else:
- rot_group_one = sidechain.ConstructFRMRotamerGroup(prot.residues[cystein_info[i][2]].GetHandle(),
- sidechain.CYD,cystein_info[i][2],
- rotamer_library,rotamer_settings)
-
- rot_group_two = sidechain.ConstructFRMRotamerGroup(prot.residues[cystein_info[j][2]].GetHandle(),
- sidechain.CYD,cystein_info[j][2],
- rotamer_library,rotamer_settings)
-
-
- else:
- if bbdep:
- rot_group_one = sidechain.ConstructRRMRotamerGroup(prot.residues[cystein_info[i][2]].GetHandle(),
- sidechain.CYD,cystein_info[i][2],
- rotamer_library,rotamer_settings,
- phi_angles[i_index],psi_angles[i_index])
-
- rot_group_two = sidechain.ConstructRRMRotamerGroup(prot.residues[cystein_info[j][2]].GetHandle(),
- sidechain.CYD,cystein_info[j][2],
- rotamer_library,rotamer_settings,
- phi_angles[j_index],psi_angles[j_index])
- else:
- rot_group_one = sidechain.ConstructRRMRotamerGroup(prot.residues[cystein_info[i][2]].GetHandle(),
- sidechain.CYD,cystein_info[i][2],
- rotamer_library,rotamer_settings)
-
- rot_group_two = sidechain.ConstructRRMRotamerGroup(prot.residues[cystein_info[j][2]].GetHandle(),
- sidechain.CYD,cystein_info[j][2],
- rotamer_library,rotamer_settings)
-
-
- frame.AddFrameEnergy(rot_group_one)
- frame.AddFrameEnergy(rot_group_two)
-
- min_index_k = -1
- min_index_l = -1
- min_score = 10000000
-
- for k in range(len(rot_group_one)):
- for l in range(len(rot_group_two)):
- score = sidechain.DisulfidScore(rot_group_one[k],rot_group_two[l],
- i_ca_pos,i_cb_pos,j_ca_pos,j_cb_pos)
- if score < min_score:
- min_index_k = k
- min_index_l = l
- min_score = score
-
- if min_score < 45:
- final_disulfid_indices.append(i_index)
- final_disulfid_indices.append(j_index)
- #create new frame residue...
- particle_list = list()
- particle_list.append(rot_group_one[min_index_k][0])
- particle_list.append(rot_group_two[min_index_l][0])
- new_frame_residue = sidechain.FrameResidue(particle_list,100000)
- frame_residues.append(new_frame_residue)
- #set the position in the proteins residues
- rot_group_one[min_index_k].ApplyOnResidue(prot.residues[i_index].GetHandle())
- rot_group_two[min_index_l].ApplyOnResidue(prot.residues[j_index].GetHandle())
-
- #we still have to add the cysteins, that are complete, even though
- #they're not participating in a disulfid bond
+ else:
if keep_sidechains:
for i,r in enumerate(prot.residues):
+ if rotamer_ids[i] == sidechain.ALA or rotamer_ids[i] == sidechain.GLY:
+ continue #no sidechain to model
try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- continue
- if rot_id != sidechain.CYS:
- continue #all other sidechains are already handled
- if i in final_disulfid_indices:
- continue #already added to the frame residues
- try:
- frame_residue = sidechain.ConstructSidechainFrameResidue(r.GetHandle(),rot_id,
+ frame_residue = sidechain.ConstructSidechainFrameResidue(r.handle,
+ rotamer_ids[i],
i,rotamer_settings)
frame_residues.append(frame_residue)
except:
incomplete_sidechains.append(i)
else:
- #The disulfid cysteins must be removed from incomplete sidechains
- for i in final_disulfid_indices:
- try:
- incomplete_sidechains.remove(i)
- except:
- pass #it's not there anyway, so we don't have to remove it
-
- elif keep_sidechains:
- for i,r in enumerate(prot.residues):
- try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- continue
- if rot_id != CYS:
- continue #all other sidechains are already handled
- try:
- frame_residue = sidechain.ConstructSidechainFrameResidue(r.GetHandle(),rot_id,
- i,rotamer_settings)
- frame_residues.append(frame_residue)
- except:
- incomplete_sidechains.append(i)
-
+ for i,r in enumerate(prot.residues):
+ if rotamer_ids[i] not in [sidechain.GLY, sidechain.ALA]:
+ incomplete_sidechains.append(i)
- #finally build complete frame
- frame = sidechain.Frame(frame_residues)
+ frame = sidechain.Frame(frame_residues)
- #build rotamers
+ #build rotamers for incomplete sidechains
for i in incomplete_sidechains:
r = prot.residues[i]
-
- try:
- rot_id = name_id_mapper[r.GetName()]
- except:
- continue
+ rot_id = rotamer_ids[i]
if(rot_id == sidechain.ALA or rot_id == sidechain.GLY):
continue
if rot_id == sidechain.CYS:
- if i in final_disulfid_indices:
- continue
rot_id = sidechain.CYH
if rot_id == sidechain.PRO:
@@ -312,19 +300,19 @@ def Reconstruct(ent, keep_sidechains = False, build_disulfids = True,
try:
if use_frm:
if bbdep:
- rot_group = sidechain.ConstructFRMRotamerGroup(r.GetHandle(),rot_id,i,
+ rot_group = sidechain.ConstructFRMRotamerGroup(r.handle,rot_id,i,
rotamer_library,rotamer_settings,
phi_angles[i],psi_angles[i])
else:
- rot_group = sidechain.ConstructFRMRotamerGroup(r.GetHandle(),rot_id,i,
+ rot_group = sidechain.ConstructFRMRotamerGroup(r.handle,rot_id,i,
rotamer_library,rotamer_settings)
else:
if bbdep:
- rot_group = sidechain.ConstructRRMRotamerGroup(r.GetHandle(),rot_id,i,
+ rot_group = sidechain.ConstructRRMRotamerGroup(r.handle,rot_id,i,
rotamer_library,rotamer_settings,
phi_angles[i],psi_angles[i])
else:
- rot_group = sidechain.ConstructRRMRotamerGroup(r.GetHandle(),rot_id,i,
+ rot_group = sidechain.ConstructRRMRotamerGroup(r.handle,rot_id,i,
rotamer_library,rotamer_settings)
except:
@@ -347,18 +335,10 @@ def Reconstruct(ent, keep_sidechains = False, build_disulfids = True,
for i,rot_group,sol in zip(residues_with_rotamer_group,rotamer_groups,solution):
try:
- rot_group[sol].ApplyOnResidue(prot.residues[i].GetHandle(),consider_hydrogens=add_polar_hydrogens)
+ rot_group[sol].ApplyOnResidue(prot.residues[i].handle,consider_hydrogens=False)
except:
print "there is a backbone atom missing... ",prot.residues[i].GetQualifiedName()
- #if we want to add polar hydrogens, we also have to consider the backbone...
- if add_polar_hydrogens:
- for r in frame_residues:
- i=r.GetResidueIndex()
- if i==100000:continue#These are cysteins that were already handled
- rh=prot.residues[i].GetHandle()
- r.ApplyOnResidue(rh,True)
-
# these methods will be exported into module
__all__ = ('Reconstruct',)