Hello,

I have some questions about refinement a protein-DNA complex structure combine 
NMR restraints and SAXS data. 
We first used the script sry_final.inp (attachment) which is from the 
eginput/deprecated/sry example in the xplor-NIH distribution to calculated 
complex structure. In this step, the DNA bases are grouped as rigid-bodies. 
Then we want to add SAXS data into this script to refine the complex structure. 
So I found the script refine.py in the eginput/saxsref example. But these two 
scripts were written in different languages, the SAXS data module could not 
directly used in the rigid-body refinement script sry_final.inp.

So I want to how to add the SAXS data in the script sry_final.inp to refine 
protein-DNA complex, because in this script we can fix the DNA bases as 
rigid-bodies. 
If it counld not work, how to fix the DNA-bases in the SAXS data script 
refine.py. 
Or if there are some better solutions by which we can both fix DNA bases and 
introduce SAXS data in the refinement.

Thanks!

Best regards.

Qianwen Li

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Attachment: sry_final.inp
Description: Binary data

xplor.requireVersion("2.25")

#
# slow cooling protocol in torsion angle space for protein G. Uses 
# NOE, RDC, J-coupling restraints.
#
# this version refines from a reasonable model structure.
#
# CDS 2005/05/10
#


(opts,args) = xplor.parseArguments(["quick"]) # check for command-line typos

quick=False
for opt in opts:
    if opt[0]=="quick":  #specify -quick to just test that the script runs
        quick=True
        pass
    pass


outFilename = "SCRIPT_STRUCTURE.sa"
numberOfStructures=100

if quick:
    numberOfStructures=3
    pass

# protocol module has many high-level helper functions.
#
import protocol
protocol.initRandomSeed(3421)   #explicitly set random seed

#
# annealing settings
#

command = xplor.command

protocol.initParams("protein")

# generate PSF data from sequence and initialize the correct parameters.
#
#from psfGen import seqToPSF
#seqToPSF('protG.seq')
#protocol.initStruct("g_new.psf") # - or from file

# generate a random extended structure with correct covalent geometry
#  saves the generated structure in the indicated file for faster startup
#  next time.
#
#protocol.genExtendedStructure("gb1_extended_%d.pdb" %
#                              protocol.initialRandomSeed())

# or read an existing model
#
protocol.loadPDB("1E8L.pdb",
                 model=49,swapProtons=True,fixMethylImpropers=True)

protocol.addUnknownAtoms()
protocol.fixupCovalentGeom(maxIters=100,useVDW=1)

#
# a PotList contains a list of potential terms. This is used to specify which
# terms are active during refinement.
#
from potList import PotList
potList = PotList()
crossTerms = PotList()

# parameters to ramp up during the simulated annealing protocol
#
from simulationTools import MultRamp, StaticRamp, InitialParams

rampedParams=[]
highTempParams=[]

# compare atomic Cartesian rmsd with a reference structure
#  backbone and heavy atom RMSDs will be printed in the output
#  structure files
#
from posDiffPotTools import create_PosDiffPot
refRMSD = create_PosDiffPot("refRMSD","name CA or name C or name N",
                            pdbFile='1E8L.pdb',
                            cmpSel="not name H*")
crossTerms.append(refRMSD)

# orientation Tensor - used with the dipolar coupling term
#  one for each medium
#   For each medium, specify a name, and initial values of Da, Rh.
#
from varTensorTools import create_VarTensor
media={}
#                        medium  Da   rhombicity
for (medium,Da,Rh) in [ ('m1',   16.11, 0.31),
                        ('m2',   13.32, 0.16) ]:
    oTensor = create_VarTensor(medium)
    oTensor.setDa(Da)
    oTensor.setRh(Rh)
    media[medium] = oTensor
    pass
    

# dipolar coupling restraints for protein amide NH.  
#
# collect all RDCs in the rdcs PotList
#
# RDC scaling. Three possible contributions.
#   1) gamma_A * gamma_B / r_AB^3 prefactor. So that the same Da can be used
#      for different expts. in the same medium. Sometimes the data is
#      prescaled so that this is not needed. scale_toNH() is used for this.
#      Note that if the expt. data has been prescaled, the values for rdc rmsd
#      reported in the output will relative to the scaled values- not the expt.
#      values.
#   2) expt. error scaling. Used here. A scale factor equal to 1/err^2
#      (relative to that for NH) is used.
#   3) sometimes the reciprocal of the Da^2 is used if there is a large
#      spread in Da values. Not used here.
#
from rdcPotTools import create_RDCPot, scale_toNH
rdcs = PotList('rdc') 
for (medium,expt,file,                 scale) in \
    [('m1','NH' ,'rdc1.tbl'       ,1),
     ('m2','NH' ,'rdc2.tbl' ,1),
     ]:
    rdc = create_RDCPot("%s_%s"%(medium,expt),file,media[medium])

    #1) scale prefactor relative to NH
    #   see python/rdcPotTools.py for exact calculation
    # scale_toNH(rdc) - not needed for these datasets -
    #                        but non-NH reported rmsd values will be wrong.

    #3) Da rescaling factor (separate multiplicative factor)
    # scale *= ( 1. / rdc.oTensor.Da(0) )**2
    rdc.setScale(scale)
    rdc.setShowAllRestraints(1) #all restraints are printed during analysis
    rdc.setThreshold(1.5)       # in Hz
    rdcs.append(rdc)
    pass
potList.append(rdcs)
rampedParams.append( MultRamp(0.01,0.3, "rdcs.setScale( VALUE )") )

# calc. initial tensor orientation
# and setup tensor calculation during simulated annealing
#
from varTensorTools import calcTensorOrientation, calcTensor
for medium in media.keys():
    calcTensor(media[medium])
#    rampedParams.append( StaticRamp("calcTensor(media['%s'])" % medium) )
    pass

# set up NOE potential
noe=PotList('noe')
potList.append(noe)
from noePotTools import create_NOEPot
for (name,scale,file) in [('dist',1,"noe-noviol.tbl"),
                          ('hb'  ,1,"hbond.tbl"),
                          #add entries for additional tables
                          ]:
    pot = create_NOEPot(name,file)
    #pot.setPotType("soft") # - if you think there may be bad NOEs
    pot.setScale(scale)
    noe.append(pot)
    pass
#noe['dist'].setPotType("soft") #some of the distance bounds are too small
rampedParams.append( MultRamp(2,100, "noe.setScale( VALUE )") )

# Set up dihedral angles
from xplorPot import XplorPot
protocol.initDihedrals("dihedral.tbl",
                       #useDefaults=False  # by default, symmetric sidechain
                                           # restraints are included
                       )
potList.append( XplorPot('CDIH') )
highTempParams.append( StaticRamp("potList['CDIH'].setScale(10)") )
rampedParams.append( StaticRamp("potList['CDIH'].setScale(200)") )
# set custom values of threshold values for violation calculation
#
potList['CDIH'].setThreshold( 5 ) #5 degrees is the default value, though



# gyration volume term 
#
# gyration volume term 
#
#from gyrPotTools import create_GyrPot
#gyr = create_GyrPot("Vgyr",
#                    "resid 1:56") # selection should exclude disordered tails
#potList.append(gyr)
#rampedParams.append( MultRamp(.002,1,"gyr.setScale(VALUE)") )

# hbdb - bb hbonds from database
#
protocol.initHBDB()
potList.append( XplorPot('HBDB') )

# Statistical torsion angle potential
#
from torsionDBPotTools import create_TorsionDBPot
torsionDBPot = create_TorsionDBPot('tDB')
potList.append( torsionDBPot )
rampedParams.append( MultRamp(.002,2,"torsionDBPot.setScale(VALUE)") )

#
# setup parameters for atom-atom repulsive term. (van der Waals-like term)
#
potList.append( XplorPot('VDW') )
rampedParams.append( StaticRamp("protocol.initNBond()") )
rampedParams.append( MultRamp(0.9,0.8,
                              "command('param nbonds repel VALUE end end')") )
rampedParams.append( MultRamp(.004,4,
                              "command('param nbonds rcon VALUE end end')") )
# nonbonded interaction only between CA atoms
highTempParams.append( StaticRamp("""protocol.initNBond(cutnb=100,
                                                        rcon=0.004,
                                                        tolerance=45,
                                                        repel=1.2,
                                                        onlyCA=1)""") )


potList.append( XplorPot("BOND") )
potList.append( XplorPot("ANGL") )
potList['ANGL'].setThreshold( 5 )
rampedParams.append( MultRamp(0.4,1,"potList['ANGL'].setScale(VALUE)") )
potList.append( XplorPot("IMPR") )
potList['IMPR'].setThreshold( 5 )
rampedParams.append( MultRamp(0.1,1,"potList['IMPR'].setScale(VALUE)") )
      

#SAXS term
from solnXRayPotTools import create_solnXRayPot
import solnXRayPotTools

xray=create_solnXRayPot('xray',experiment='lsz_5.0mgmL_saxswaxs.dat',
                        numPoints=50,
                        useInternalSpline=True,
                        normalizeIndex=-3,preweighted=False)

xrayCorrect=create_solnXRayPot('xray-c',experiment='lsz_5.0mgmL_saxswaxs.dat',
                               numPoints=50,
                               useInternalSpline=True,
                               normalizeIndex=-3,preweighted=False)

solnXRayPotTools.useGlobs(xray)

xray.setNumAngles(50)
xrayCorrect.setNumAngles(500)
xray.setScale(40)
xray.setCmpType("plain")
potList.append(xray)
crossTerms.append(xrayCorrect)

print xray.calcEnergy()
from solnScatPotTools import fitParams

#correct I(q) to higher accuracy, and include solvent contribution corrections
#stride=10 specifies that this fit is performed every 100th temperature during
#simulated annealing. During refinement, infrequent solvent correction updates
#are ok because the structure doesn't change too much.
#
rampedParams.append(
    StaticRamp(
    "fitParams(xrayCorrect);xray.calcGlobCorrect(xrayCorrect.calcd())",
    stride=100))

# Give atoms uniform weights, except for the anisotropy axis
#
protocol.massSetup()


# IVM setup
#   the IVM is used for performing dynamics and minimization in torsion-angle
#   space, and in Cartesian space.
#
from ivm import IVM
dyn = IVM()

# initially minimize in Cartesian space with only the covalent constraints.
#   Note that bonds, angles and many impropers can't change with the 
#   internal torsion-angle dynamics
#   breaks bonds topologically - doesn't change force field
#
#dyn.potList().add( XplorPot("BOND") )
#dyn.potList().add( XplorPot("ANGL") )
#dyn.potList().add( XplorPot("IMPR") )
#
#dyn.breakAllBondsIn("not resname ANI")
#import varTensorTools
#for m in media.values():
#    m.setFreedom("fix")                 #fix tensor parameters
#    varTensorTools.topologySetup(dyn,m) #setup tensor topology
#
#protocol.initMinimize(dyn,numSteps=1000)
#dyn.run()

# reset ivm topology for torsion-angle dynamics
#
dyn.reset()

for m in media.values():
    m.setFreedom("fixDa, fixRh")        #fix tensor Rh, Da, vary orientation
#    m.setFreedom("varyDa, varyRh")      #vary tensor Rh, Da, vary orientation
protocol.torsionTopology(dyn)

# minc used for final cartesian minimization
#
minc = IVM()
protocol.initMinimize(minc)

for m in media.values():
    m.setFreedom("varyDa, varyRh")    #allow all tensor parameters float here
    pass
protocol.cartesianTopology(minc)



# object which performs simulated annealing
#
from simulationTools import AnnealIVM
init_t  = 3000.     # Need high temp and slow annealing to converge
cool = AnnealIVM(initTemp =init_t,
                 finalTemp=25,
                 tempStep =12.5,
                 ivm=dyn,
                 rampedParams = rampedParams)

def accept(potList):
    """
    return True if current structure meets acceptance criteria
    """
    if potList['noe'].violations()>0:
        return False
    if potList['rdc'].rms()>1.2: #this might be tightened some
        return False
    if potList['CDIH'].violations()>0:
        return False
    if potList['BOND'].violations()>0:
        return False
    if potList['ANGL'].violations()>0:
        return False
    if potList['IMPR'].violations()>1:
        return False
    
    return True

def calcOneStructure(loopInfo):
    """ this function calculates a single structure, performs analysis on the
    structure, and then writes out a pdb file, with remarks.
    """

    # initialize parameters for high temp dynamics.
    InitialParams( rampedParams )
    # high-temp dynamics setup - only need to specify parameters which
    #   differfrom initial values in rampedParams
    InitialParams( highTempParams )

    # high temp dynamics
    #
    protocol.initDynamics(dyn,
                          potList=potList, # potential terms to use
                          bathTemp=init_t,
                          initVelocities=1,
                          finalTime=150,    # stops at 150ps or 15000 steps
                          numSteps=15000,   # whichever comes first
                          printInterval=100)

    dyn.setETolerance( init_t/100 )  #used to det. stepsize. default: t/1000 
    dyn.run()

    # initialize parameters for cooling loop
    InitialParams( rampedParams )


    # initialize integrator for simulated annealing
    #
    protocol.initDynamics(dyn,
                          potList=potList,
                          numSteps=400,       #at each temp: 400 steps or
                          finalTime=1 ,       # 1 ps, whichever is less
                          printInterval=100)

    # perform simulated annealing
    #
    cool.run()
              
              
    # final torsion angle minimization
    #
    protocol.initMinimize(dyn,
                          printInterval=50)
    dyn.run()

    # final all- atom minimization
    #
    protocol.initMinimize(minc,
                          potList=potList,
                          dEPred=10)
    minc.run()

    #do analysis and write structure
    loopInfo.writeStructure(potList)
    pass



from simulationTools import StructureLoop, FinalParams
StructureLoop(numStructures=numberOfStructures,
              pdbTemplate=outFilename,
              structLoopAction=calcOneStructure,
              genViolationStats=1,
              averagePotList=potList,
#              averageSortPots=[potList['BOND'],potList['ANGL'],potList['IMPR'],
#                               noe,rdcs,potList['CDIH']],
              averageCrossTerms=crossTerms,
              averageTopFraction=0.2, #report only on best 50% of structs
              averageContext=FinalParams(rampedParams),
              averageFilename="SCRIPT_ave.pdb",    #generate regularized ave structure
              averageFitSel="name CA",
              averageCompSel="not resname ANI and not name H*"     ).run()



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