Hello,
I would like to use a refinement protocol against ensembles of different
sizes (2, 4 ,6, 8, 10) for a multidomain protein (a tandem of SH2s
domains, one SH3 and one splitPH domain separated by flexible linkers).
I'm using restraints from SAXS intensities and chemical shift
perturbations for the interaction surface between the splitPH and one of
the SH2 domains.
When I run the script below, which has been adapted from SAXS_EI
protocol in the eginput xplor-nih2.29 directory, XPLOR crashes at
different stages of the protocol generating a number of error messages
(such as : /dms/prog/src/xplor-nih/bin/xplor: line 525: 1401
Segmentation fault).
Does anyone have any suggestion on how to solve this problem? Thanks for
your help.
numberOfStructures = 2 #number of structure to calculate
import protocol
protocol.initRandomSeed(63342)
from glob import glob
startStructures=glob("dock_*.pdb")
ensembleSize = 2 # 2, 4, 6, 8, 10 members
import simulation
sim = xplor.simulation
pdbTemplate="SCRIPT_%d_STRUCTURE_MEMBER.fit" % ensembleSize
# create Simulation with ensembleSize ensemble members
from ensembleSimulation import EnsembleSimulation
esim = EnsembleSimulation("ensemble",ensembleSize)
protocol.loadPDB("SA.pdb",deleteUnknownAtoms=True) # generate psf from
starting structure
splitPH = "resid 488:521 or resid 874:933"
SH3 = "resid 790:852"
SH2s = "resid 549:768"
SASel = "resid 488:521 or resid 549:768 or resid 790:852 or resid 874:933"
# splitPH/SH2 perturbed residues
spPHsc = "((resid 489:490 or resid 493 or resid 502 or resid 506 or
resid 508:509 or resid 511 or resid 518:521 or resid 874:876) and (not
(name n or name c or name ca or name o or name hn or name ha)))"
cSH2sc = "((resid 668:671 or resid 694:695 or resid 702 or resid 718:723
or resid 726 or resid 730 or resid 732:733) and (not (name n or name c
or name ca or name o or name hn or name ha)))"
from potList import PotList
potList = PotList()
crossTerms=PotList('cross terms')
crossTerms=PotList('cross terms')
from simulationTools import StaticRamp, MultRamp
from simulationTools import InitialParams, FinalParams
rampedParams=[]
highTempParams=[]
from avePot import AvePot
from xplorPot import XplorPot
# set up NOE potential
noe=PotList('NOE')
potList.append(noe)
from noePotTools import create_NOEPot
for (name,scale,file) in [('inte',1,"interface.tbl"),
]:
pot = AvePot(create_NOEPot(name,file))
pot.setAveType("sum")
pot.setPotType("soft") # - if you think there may be bad NOEs
pot.setScale(scale)
noe.append(pot)
rampedParams.append( MultRamp(2,100, "noe.setScale( VALUE )") )
# setup parameters for atom-atom repulsive term. (van der Waals-like term)
vdw = AvePot(XplorPot, "VDW")
potList.append(vdw)
rampedParams.append( StaticRamp("""protocol.initNBond()""") )
rampedParams.append( MultRamp(0.9,0.8,
"xplor.command('param nbonds repel VALUE end
end')") )
rampedParams.append( MultRamp(.004,4,
"xplor.command('param nbonds rcon VALUE end
end')") )
highTempParams.append( StaticRamp("""protocol.initNBond(rcon=0.1,
repel=1.2,
onlyCA=1)""") )
from solnXRayPotTools import create_solnXRayPot
import solnXRayPotTools
xray=create_solnXRayPot('xray',experiment='saxs.data',
numPoints=30, # originally used 100 points
maxQ=0.2,
normalizeIndex=-3,preweighted=False)
xrayCorrect=create_solnXRayPot('xray-c',experiment='saxs.data',
numPoints=30,
maxQ=0.2,
normalizeIndex=-3,preweighted=False)
solnXRayPotTools.useGlobs(xray)
xray.setNumAngles(50)
xrayCorrect.setNumAngles(500)
xray.setScale(400)
xray.setCmpType("plain")
potList.append(xray)
crossTerms.append(xrayCorrect)
print xray.calcEnergy()
from solnScatPotTools import fitParams
#corrects I(q) to higher accuracy, and include solvent contribution
corrections
rampedParams.append( StaticRamp("fitParams(xrayCorrect)") )
rampedParams.append(
StaticRamp("xray.calcGlobCorrect(xrayCorrect.calcd())") )
# Ratio of gyration potential
protocol.initCollapse("resid 488:933",
Rtarget=32) # approximate value from Guinier analysis
rgyr = AvePot(XplorPot, 'COLL')
potList.append(rgyr)
#RAP term to keep members of ensemble in similar orientations
from posRMSDPotTools import RAPPot
rap = RAPPot("rap","(name ca and resid 488:933)")
rap.setScale( 100.0 )
rap.setPotType( "square" )
rap.setTol( 25.0 ) #25A square well potential for members orientations
potList.append(rap)
crossTerms.append(rap)
#measure of difference between ensemble members
posRMSD = RAPPot("posRMSD","""(name ca and resid 488:933)""")
crossTerms.append(posRMSD)
#Xplor potentials
protocol.initRamaDatabase(type='protein')
rama = AvePot(XplorPot,'RAMA')
potList.append(rama)
rampedParams.append( MultRamp(.002,1,"potList['RAMA'].setScale(VALUE)") )
bond = AvePot(XplorPot,"BOND")
potList.append(bond)
angl = AvePot(XplorPot,"ANGL")
potList.append(angl)
rampedParams.append( MultRamp(0.4,1,"potList['ANGL'].setScale(VALUE)") )
impr = AvePot(XplorPot,"IMPR")
potList.append(impr)
rampedParams.append( MultRamp(0.1,1,"potList['IMPR'].setScale(VALUE)") )
protocol.massSetup()
from ivm import IVM
dynRigid = IVM()
dynRigid.fix("(%s) and not (%s)" % (SH2s,cSH2sc))
dynRigid.group("(%s) and not (%s)" % (splitPH,spPHsc)) #leaves the
perturbed sc free
dynRigid.group("(%s)" % SH3)
protocol.torsionTopology(dynRigid)
from simulationTools import AnnealIVM
init_t = 3000
cool = AnnealIVM(initTemp =init_t,
finalTemp=25,
tempStep =25,
ivm=dynRigid,
rampedParams = rampedParams)
def calcOneStructure(loopInfo):
""" this function calculates a single structure, performs analysis
on the
structure, and then writes out a pdb file, with remarks.
"""
InitialParams( rampedParams )
InitialParams( highTempParams )
#initial minimization
protocol.initMinimize(dynRigid,
potList=potList,
numSteps=1000,
printInterval=200)
dynRigid.run()
#high-temp dynamics
protocol.initDynamics(dynRigid,
potList=potList,
bathTemp=init_t,
initVelocities=1,
finalTime=800, # stops at 800ps or 8000 steps
numSteps=8000, # whichever comes first
printInterval=200)
dynRigid.setETolerance( init_t/100 ) #used to det. stepsize.
default: t/1000
dynRigid.run()
# initialize parameters for cooling loop
InitialParams( rampedParams )
# initialize integrator for simulated annealing
#
protocol.initDynamics(dynRigid,
potList=potList,
numSteps=100, #at each temp: 100 steps or
finalTime=.2 , # .2ps, whichever is less
printInterval=100)
# perform simulated annealing
#
cool.run()
# final torsion angle minimization
#
protocol.initMinimize(dynRigid)
dynRigid.run()
#do analysis and write structure
loopInfo.writeStructure(potList)
pass
from simulationTools import StructureLoop, FinalParams
StructureLoop(numStructures=numberOfStructures,
pdbTemplate=pdbTemplate,
structLoopAction=calcOneStructure,
genViolationStats=True,
averageFilename="SCRIPT_ave.pdb",
averageRegularize=False,
averagePotList=potList,
averageCrossTerms=crossTerms,
averageTopNum=20, #report on the top 20 structs
averageFitSel="name CA and (%s)" % SH2s,
averageContext=FinalParams(rampedParams)).run()
--
Dr Diego Esposito
Division of Molecular Structure
The National Institute for Medical Research
The Ridgeway, Mill Hill
London, NW7 1AA, United Kingdom
Tel off +44 (0)20 88162066
Tel lab +44 (0)20 88162145
Fax +44 (0)20 88162734
Fax +44 (0)20 89064477
