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MolDyn |
RUN program by the command
../$MDYN07HOME/mDynQ07 -i inProtcol -c inPDB [-mdR mdRestXYZVin] [-mv moveRes]
[-r1 inRestrainA1 ] [-r2 inRestrainA2] [-rB rigBodyFile]
[-sa saProtocol] [-mn molName] [-mdX mdFinalPDB] -o runOutFile [-er errorFile]
in parenthesis [ ] are uxilarry files. The auxilary files will be used by program if the main command file
defines respective task.
Command line DESCRIPTION:
-i inProtcol : file MdynPar.inp defines protocol for the mDyn particular Run
-c inPDB : file of the initial molecular structure as molec.pdb file in the PDB format
-mdR mdRestXYZVin : XYZ+Velocity file to REstart MD from the last snapshot file XYZV , see exaple t5
1arb.mdXYZVfin0001.pdb it is USED with $mdRestart keyword in command file
inProtcol
NOTE! the initial XYZ will be taken from mdRestXYZVin file !
the PDB file inPDB is not USED with the key -mdR
-r1 inRestrainA1 : file defines of positional restraints for atoms of the molecule
-r2 inRestrainA2 : file defines atom-atom distance restraints
-rB rigBodyFile : file defines rigid body segments of the main chain of protein
-mv moveRes : file defines List of moving Residues
-sa saProtocol : file defines simulated annealing protocol
-mn molName : character set defining molecula name. molName. will be attached to RESULT files
-o runOutFile : run output file
-mdX mdFinalPDB : final PDB file of the Energy/MD optimization
Current status of program run is printed on the standart output device (consol) or
can be redirected to user defined file or can be defined in the argument line:
-er errorFile : error message file : they are dublicated in the runOutFile
#
if file name definition in the argument line is missing for a file
than the default name is used for this file
NOTE! if the command line does not include a key -X , while the command file defines task which need data file coupled with -X keyword, than program try to find default (standart) name data file in the current directory.
Default names:
#
inProtcol = ./MdynPar.inp
inPDB = ./molec.pdb
mdRestXYZVfile = ./mdXYZVin.pdb
moveRes = ./moveRes.inp
inRestrainA1 = ./restrAt1.inp'
inRestrainA2 = ./restrAt2.inp'
rigBodyFile = ./rigBody.inp
saProtocol = ./SAprotocol.inp
molName = space
runOutFile = ./mDynSB.out
errorFile = ./mDynSB.err
mdFinalPDB = ./molMdFin.pdb
#
inProtcol = ./MdynPar.inp
The nain command file consist of lines with command keyword.
Keyword start with $ sign in the first position of line
One Keyword in line
#example of MdynPar.inp file and keyword description
# MdynPar.inp
$OUTfull ! full extended output of program run
#Initial PDB data quality
$Hread ! read INPUT pdb file with Hydrogens
! by default OUTshort option is ON
# DEfinition of OPtimized segments of protein:
$fullProtMD ! full molecule is flexible
#$MovingRes ! defines List of opimized segments
#FORCE FIELD MODIFICATIONS:
#
$shake=2 ! all valence bobds are fixed by shake method
$zeroRot ! exclude translation and rotation of the molecule
as rigid body
$hBond128 = 2.0 ! scaling coeff for H-bonds
! default=1.0 it is standart force field
$harmAt1PosRst=0.25 !invoke restraintsA1 type =
positional harmonic restraints for atom position
with harmConst (kcal/A^2).
program need a special file -r1 restrA1File
which defines restrained segmants of protein
see additional description
$distRestrA2 !invoke restraintsA2 type atom-atom distances
for user defined pairs of atoms in the file
-r2 restrA2File (see additional description)
$rigBody !invoke optimization with frozen internal structure of
protein main chain for user defined segments of sequence
need file -rB rigidBodySegment (see additional description)
$compactForce = 0.5 ! invoke additional compactization forces
! to accelerate protein folding
#
$aSoftCore = 0.5 !invoke SOFTNES for the van der waals atom-atom potential
! at the small (contact) atom-atom distances
! Use of the softCore VDW potential helps to optimize
! BAD molecular structures with many spartial atom-atom clashes
! values range 0 - 1 from very Soft to standart VDW
#SOLVATION MODEL
$SolvMod = GShell
#
#
# OPIMIZATION PROTOCOL:
$engCalc ! do energy calculation
$engOptim ! do energy optimization by local Optimizer
$nOptStep=1 !max N optim steps
#
#PROTOCOL for Molecular Dynamics:
$doMDyn ! do MolDynamics
$MDSA !do MolecularDynamis SimAnnealing
needs SAprotocolFile -sa saProtocol File,
see additional description
#
#PROTOCOL of MD equilibration:
#
$initMDTemp=50.00 !initial Temperature to start MolDyn
$bathMDTemp=50.00 !thermostat temperature of thermostat i.e. target temperature
$runMDnstep=2000 !number of time-steps for MD simulation
$mdTimeStep=0.002
#
$NTV=1 ! MD ensemble definition
#
#
# MD Trajectory writing:
$nwtra=500
$WRpdb ! write snarshort structures in the PDB format
! default WRpdbq OPTion is ON : extended PDB format
! PDB + Qatom
#
END
#
NOTE that parameter file formatted, i.e. $ sign should be the firs character of the line
----------------------------------------------------------------------------
KEYWORD LIST:
keyw = 'OUTfull'
keyw = 'WRpdb'
keyw = 'Hread'
keyw = 'fullProtMD'
keyw = 'MovingRes'
keyw = 'LigRes'
keyw = 'doLigDock'
keyw = 'MDSA'
keyw = 'SolvMod'
keyw = 'zeroRot'
keyw = 'hBond128'
keyw = 'harmAt1PosRst'
keyw = 'distRestrA2'
keyw = 'compactForce'
keyw = 'shake'
keyw = 'engCalc'
keyw = 'engOptim'
keyw = 'nOptStep'
keyw = 'aSoftCore'
keyw = 'initMDTemp'
keyw = 'bathMDTemp'
keyw = 'mdTimeStep'
keyw = 'runMDnstep'
keyw = 'doMDyn'
keyw = 'mdRestart'
keyw = 'NTV'
keyw = 'nwtra'
-----------------------------------------------------------------------------
KEYWORD DESCRIPTION:
#OUTPUT DETAILES:
$OUTfull ! full extended output of program run
! by default OUTshort option is ON
#
# INPUT PDB FILE DETAILES:
$Hread ! defines that all Hydrogens will be read from input molecule structure -c inPDB file
otherwise the ALL HYDrogens will be restored by the program, i.e.
all H atoms will be deleted and added according to molecular topology for RESidues.
Using Library in the ./dat/h_add.dat
NOTE! it is recommended start to works with a new protein without option $Hread even if the PDB
file has all hydrogen atoms, because the hydrogen atom names for protein side chains
have multiple definition in the PDB data base.
It is better if mDyn program will add all hydrogens to the heavy atoms.
#DEFINITION OF OPTIMIZED RESIDUES:
$fullProtMD !defines FULL (i.e. ALL atoms) of the USER molecule
will be free to move in energy relaxation or molDyn
$MovingRes ! logical keyWord defines that only a defined set of RESidue are free
this keyWord is coupled with file -mv moveRes in the argument line to start
the program
default name for moveRes file is ./moveRes.inp
#EXAMPLE of ./moveRes.inp
#1arb
aaaaaaIIIIiiii
#
MOVRES 1 10 !line defines first and last resudue of moving segments integers devided by space
MOVRES 45 76
MOVRES 115 260
end !end or END should be last line if the file
************
#FORCE FIELD DEFINITION:
$hBond128 = 2.0 ! scaling coeff for H-bonds
$aSoftCore = 0.5 !invoke van der waals atom-atom potential with modified
! SoftCore at the small (contact) atom-atom distances
! SoftCore modification is used for energyOPtimization
and MD equilibration stages.
! Use of the softCore VDW potential helps to optimize
! BAD structures with many starical atom-atom clashes
! values range 0 - 1 from very Soft to standart VDW
$harmAt1PosRst=0.25 ! digital keyWord define RESidue segments with 1 atom position harmonic
restrants.
0.25 = harmonic restrain Constant K
restrEnergy = 0.5*K(r - r0)**2,
the reference position r0 = initialXYZinput.pdb - positions from
the initial INPut PDB file which defines INItial structure of molecule
this keyWord is coupled with file -r1 inRestrainA1 of the argument line to start
the program mdyn
default name for inRestrain file is ./restrAt1.inp
#EXAMPLE of inRestrainA1 file:
#harmonically restrained RESidue segments
#xxxxxIIIIiiiiaaAAA
#(6x,2i4,a40)
RESTA1 1 63 PBB ! line starts from keyWord RESTAT numbers=first/last residue of segment
! PBB (only protein backbone atoms are restrained, i.e. side chains are free)
RESTA1 78 120 ALL ! ALL (all atoms are restrained)
! integers and words are devided by space
end
# ---------------------------------------------------
$distRestrA2 ! defines optimization/MD with atom-atom dist RestrainA2
! needs file [-r2 inRestrainA2] in command line
-r2 inRestrainA2 : default name : restrAt2.inp
#
EXAMPLE of inRestrainA2 file:
#harmonically restrained Atom-Atom distances
#xxxxxx
#keyword atom1 atom2 distA HarmConst(kcal/mol*A^2)
RESTA2 ND2 ASN 222 : OG1 THR 219 = 7.0 1.5
RESTA2 O GLY 170 : OG1 THR 219 = 8.0 2.5
RESTA2 OH TYR 109 : OG1 THR 111 = 7.5 3.0
END
#----------------------------------------------------
$rigBody !defines optimizatiom/MD considering some segments of the main chain
! as a rigid body.
! The List of rigid segments of the main chain is user defined.
! Each segment will keep rigid internal structure of the protein main chain,
! has rotatational and translational degrees of freedom.
! The side chains of the rigid segments are flexible.
#Needs file rigidBody.inp
#EXAMPLE of rigidBody.inp file:
#
RIGB01 11 16 !line defines first and last resudue of moving segments integers devided by space
RIGB02 47 59
RIGB03 77 99
end !end or END should be last line if the file
# - - - - - - - - - - - - - - - - - - - - - - - - -
$compactForce = 0.25 ! define additional compactization forces for protein atoms
! Recomended forceParameter = 0.1 - 1.0
# --------------------------------------------------
$shake=2 ! invoke shake subroutine to keep bonds fixed. =1 -bonds with Hydrogen, =2 all bonds
----------------------------------------------------
#Defining of the SOLVation model:
there are 4 variants of Implicit models
1 variant of Explicit model
#:
$SolvMod = GShell ! implicit Gaussian Shell solvation model
$SolvMod = GShell + WBrg ! implicit Gaussian Shell solvation model + WaterBridges between polar atoms
! WaterBridges descride solvent mediated interactions trough stong bound water
! molecules via implicit model of water bridges
$SolvMod = GBorn ! implicit Generalized Born model + SAS HydroPhobic solvation
$SolvMod = GBorn + WBrg ! implicit Generalized Born model + SAS HydroPhobic solvation + WaterBridges
$Solv = ExWshell 4.5 [A] ! explicit water shell of 4.5 Angst around protein;
! recomended thikness 3.0 - 6.0 A
---------------------------------------------------
$mdRestart ! restart molDynamics from a snapshot [molName.]mdXYZVfin000N.pdb
the file [molName.]mdXYZVfin000N.pdb should be copied to the file mdyn Restart file
mdXYZVin.pdb
$doMDyn ! do molecular dynamics
$MDSA ! do Molecular Dynamical Simulated Annealing
! coupled with file -sa SAprotocol which define protocol of the simulated annealing
#EXAMPLE of Aprotocol.inp file
#SA protocol
#nSAstep 2
#(f10.1,1x,f8.1,1x,3(f6.1,1x)
# nMDstep tempTg SCvdW wfHb128BB wfhB128BS
SAPROT 100000 500.0 0.8 1.0 1.0 !line starts from keyword SAPROT
SAPROT 100000 100.0 1.0 1.0 1.0
END
#
nMDstep - number of md timeStep
tempTg - target temperature in K, this temperature will be reach during ntimeMX steps
SCvdW - parameter 0 - 1 to define softness of the van der waals potential. Soft potential
modifies Potential Energy Surface and decrease barriers of conformational transitions
wfHb128BB,
wfhB128BS - (1 - 0) scaling factors for BackBone-BackBone and
BackBone-SideChain Hydrogen Bond energy
#--------------------------------------------------
#
# OPIMIZATION PROTOCOL:
$engCalc ! do energy calculation
$engOptim ! do energy optimization by local Optimizer
$nOptStep=1 !max N optim steps
#
#PROTOCOL for Molecular Dynamics:
$doMDyn ! do MolDynamics
$MDSA !do MolecularDynamis SimAnnealing
needs SAprotocolFile -sa saProtocol File,
#MD EQUILIBRATION:
$initMDTemp=50.00 !defines initial temperature to start MD
! recommended low temperature < 50K
! temperature can be steadelly increased to the 300K and higher
! USING $MDSA option
$bathMDTemp=50.00 ! bath temperature in the MD equilibration run
$runMDnstep=2000 ! number of MD time steps in the equilibration run
$mdTimeStep=0.002 ! value of the MD time step in ps,
! recomended 0.001 - 0.002
$NTV=1 ! ansemble NTV=0/1
! =1 md run with constant T
#MD TRAJECTORY WRITING
$nwtra=500 ! structure XYZ (snapshot) will be written
!as a series of molMdResXXXX.pdb files
$WRpdb ! write snapshort structures in the PDB format
! default is WRpdbq OPTion is ON : extended PDB format
! PDB + Qatom column
#* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
#
-c inPDB file - standart pdb file
#EXAMPLE of inPDB file:
****************************************************************************************
NOTE! it is recommended to start to work with a new protein without option $Hread even if the PDB
file has all hydrogen atoms, because the hydrogen atom names for protein side chains
have multiple definition in the PDB data. It is better if mDyn program will add all hydrogens
to the heavy atoms.
*******************************************************************************************
REMARK: PDB:
ATOM 1 N GLY A 1 11.726 -10.369 10.598
ATOM 2 H1 GLY A 1 11.921 -11.015 9.807
ATOM 3 H2 GLY A 1 12.518 -10.395 11.271
ATOM 4 H3 GLY A 1 10.852 -10.663 11.079
ATOM 5 CA GLY A 1 11.567 -9.015 10.090
ATOM 6 HA2 GLY A 1 10.772 -8.977 9.420
ATOM 7 HA3 GLY A 1 12.439 -8.710 9.612
ATOM 8 C GLY A 1 11.280 -8.099 11.303
ATOM 9 O GLY A 1 11.256 -8.584 12.493
ATOM 10 N VAL A 2 11.060 -6.876 11.020
ATOM 11 H VAL A 2 11.066 -6.574 10.025
etc.
TER ! CHAIN TERmination
ATOM 1302 N GLY A 94 10.957 -15.678 12.832
ATOM 1303 H GLY A 94 10.735 -14.663 12.877
ATOM 1303 H GLY A 94 10.735 -14.663 12.877
ATOM 1304 CA GLY A 94 10.193 -16.559 11.950
ATOM 1305 HA2 GLY A 94 9.428 -16.004 11.516
ATOM 1306 HA3 GLY A 94 9.784 -17.323 12.525
ATOM 1307 C GLY A 94 11.016 -17.184 10.843
...
etc.
TER ! CHAIN TERmination
END ! file END
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
#
# PDB mDyn trajectory file description:
#
Program mDyn generate a series of snapshot files, e.g., 1arb.molMdRes0nnn.pdb (test/t4)
the molMdResXXXX.pdb file (see example) contains all atomic coordinates and additional information
in the REMARK: lines
####
REMARK: Md result : MdTime(ps): 2.4940
REMARK: $nstep: 1247
REMARK: $nRecPDB: 5
REMARK: RMSD(x0): 0.43 <- RMSD all atom
REMARK: badBond: n,erAv(A) : 0 0.000 <- number and error Average for bond length in Angstrem
REMARK: badAng : n,erAv(grd): 8 9.42 <- number and error Average for bond angles in grad
# ENERGY TERMS for the given structure
REMARK: $ENERGY: :Kcal
REMARK: eVbondDef: 100.89315 <-bond deformation energy
REMARK: eVangDef : 441.63705 <-angle deformation energy
REMARK: eImpDef : 35.68147 <-Improper torsion agle [planarity] energy
REMARK: eTorsDef : 691.25769 <-torsion potentioal energy
REMARK: engVDWR1 : -1031.16211 <- van der waals energy for cutoff R1=8 A
REMARK: ehBHxY128: -608.70599 <- H-bondinds energy
REMARK: engCOULR1: -816.25323 <- COULOMBIC for distances < cutoff R1
REMARK: engCOULR2: -4.47208 <- COULOMBIC for distances Rij, R1< rij
To run Ligand docking modules, the main command file MdynPar.inp have to include the next keywords: # keywords=value $LigRes= 282 283 !define start/end ligandResidues
in the inPDB file [(i4,1x,i4) format after= ] !the residues numbers are the same as it is in the initial !inPDB file [united pdb file of protein + ligand] $doLigDock=1 !run docking for USER defined initial position of Ligand ! as it is in the initial inPDB file [united pdb file of protein + ligand] ! Docking is done via simulated annealing molDynamics ! with coupled temperature and force field variation. ! Ligand CMass can move in vicinity of initial ! position +/- 4.0 A ! Orientational global optimization are done via ! simulated annealing MD with multiple start ! orientations. Initial orientations are uniformly ! cover all orientational phase space with distance = 90 deg $doLigDock=2 ! run ab initio docking ! This option will seach all binding sites on the ! protein molecular surface including cavities and crevices. ! 1) search of surface cavities, crevicies and groovs ! 2) calculation and scoring of binding site candidate ! positions based on the number of ligand-protein atom-atom contacts. ! 3) ligand docking by simulated annealing molecular dynamics for best ! candidate binding sites. #REMARKS: 1) -c inPDBfile in command line should include proteinXYZ + ligandXYZ. it is recomended to make initial Ligand XYZ in the file inPDBfile in a contact vicinity of Protein. 2) For a new Ligand, the Ligand molecular topology SHOULD BE included into the LIBrary topology file bs_one_all94.dat at the moment the topology LIB includes the next Ligands # DOCK TEST#1 ./1bty - trypsine-benzamidine complex 1bty.ben.Native.pdb - protein-lig complex with NATIVE binding mode for Ligand 1bty.ben.notNative.pdb - protein-lig complex with notNATIVE (arbitryry) mode for Ligand the both files can be used as inPDB file MdynPar_1bty.inp moveRes_1bty.inp SAprotocol_1bty.inp : INPUT files to define JOB protocol # #Run the mDyn program: > $MDYN07HOME/mDynQ07 -i 1bty_MdynPar.inp -c 1bty.ben.notNative.pdb -sa SAprotocol_1bty.inp -mv moveRes_1bty.inp -mn 1bty -o 1bty.out # UNDESTANDING DOCKING RESULTS: Program creates a files in current job directory: 1) file 1bty.bSiteAtOnSAS00.pdb shows XYZ positions of binding site candidates on the protein surface scored by contact score ~ number of protein atoms in a vicinyty of the binbing site. #LigBindGridOnSAS: bindSite XYZ contactScore ATOM 1 LBSt 1 16.536 26.130 8.764 11 ATOM 2 LBSt 2 29.319 14.972 16.378 11 ATOM 3 LBSt 3 6.595 15.454 32.366 9 ATOM 4 LBSt 4 28.049 26.396 3.572 9 ATOM 5 LBSt 5 37.370 14.662 29.278 8 ATOM 6 LBSt 6 9.605 28.662 39.481 7 ATOM 7 LBSt 7 18.280 35.574 15.402 7 ATOM 8 LBSt 8 30.648 34.679 44.060 7 ATOM 9 LBSt 9 34.040 33.767 21.484 7 ATOM 10 LBSt 10 5.056 19.922 18.987 6 ATOM 11 LBSt 11 25.308 5.865 13.437 6 ATOM 12 LBSt 12 13.241 31.812 30.019 6 ... ATOM 40 LBSt 40 25.260 6.929 29.909 4 ATOM 41 LBSt 41 26.781 13.047 43.008 4 Docking alhorithm put ligand center into each of the positions with SCore >= 6 and refine ligand position&orientation and conformation via global optimization by Simulated annealing coupled with protein-Ligand force field deformation. # The resulting ligand positions are collected in the files : 1bty.LigDockFin000.001.pdb 1bty.LigDockFin000.002.pdb 1bty.LigDockFin000.003.pdb 1bty.LigDockFin001.001.pdb 1bty.LigDockFin001.002.pdb 1bty.LigDockFin001.003.pdb ... 1bty.LigDockFin015.003.pdb # File 1bty.LigDockFin_ePL.res : collects the refined total Potential energy of Lig-Lig + Lig-Prot interactions for Ligand Docking modes: # NN LigDockFinXXX.XXX.pdb ePLtot eVDW eCoul eHb eGeo eSolv tempTAv 1 ./LigDockFin000.001.pdb -26.2 -4.9 -7.7 -9.6 -6.1 2.2 56.1 2 ./LigDockFin000.002.pdb -25.7 -2.9 -9.6 -9.7 -6.3 2.8 56.1 3 ./LigDockFin000.003.pdb -25.3 -3.7 -8.8 -9.6 -5.8 2.7 56.1 4 ./LigDockFin001.001.pdb -25.9 -9.0 -1.7 -9.5 -10.2 4.5 56.9 5 ./LigDockFin001.002.pdb -21.6 -9.3 0.7 -4.6 -11.5 3.2 56.9 6 ./LigDockFin001.003.pdb -21.5 -9.7 -0.5 -9.1 -4.3 2.2 56.9 7 ./LigDockFin002.001.pdb -42.5 -18.6 -8.1 -11.2 -8.6 3.9 51.9 !best1 mode =native 8 ./LigDockFin002.002.pdb -42.4 -21.0 -6.6 -10.5 -8.0 3.8 51.9 9 ./LigDockFin002.003.pdb -42.0 -18.5 -8.6 -11.9 -8.2 5.2 51.9 10 ./LigDockFin003.001.pdb -15.7 -6.7 1.2 -4.9 -7.3 2.0 46.2 11 ./LigDockFin003.002.pdb -14.9 -7.5 1.2 -4.8 -7.2 3.5 46.2 12 ./LigDockFin003.003.pdb -13.7 -5.7 2.1 -4.4 -8.2 2.6 46.2 13 ./LigDockFin004.001.pdb -26.1 -4.7 -8.1 -9.8 -6.2 2.6 49.8 14 ./LigDockFin004.002.pdb -25.5 -6.1 -6.1 -9.6 -6.0 2.3 49.8 15 ./LigDockFin004.003.pdb -25.5 -4.8 -7.0 -9.8 -5.2 1.3 49.8 16 ./LigDockFin005.001.pdb -31.3 -12.0 -5.0 -9.5 -7.7 2.9 55.5 17 ./LigDockFin005.002.pdb -30.7 -11.2 -5.0 -9.7 -7.4 2.6 55.5 18 ./LigDockFin005.003.pdb -30.7 -12.3 -5.0 -9.5 -7.3 3.4 55.5 19 ./LigDockFin006.001.pdb -19.8 -7.7 -2.7 -4.9 -7.1 2.6 49.3 20 ./LigDockFin006.002.pdb -18.7 -10.2 -2.5 -4.8 -7.9 6.6 49.3 21 ./LigDockFin006.003.pdb -18.7 -9.1 1.8 -7.9 -7.4 3.8 49.3 22 ./LigDockFin007.001.pdb -20.9 -8.8 0.5 -9.6 -5.5 2.5 58.5 23 ./LigDockFin007.002.pdb -20.7 -8.9 1.2 -10.5 -5.6 3.2 58.5 24 ./LigDockFin007.003.pdb -20.1 -7.6 1.3 -10.8 -4.9 2.0 58.5 the file 1bty.LigDockFin*.pdb also keeps the final potential energies of docking modes: # 1bty.LigDockFin000.001.pdb:engPOTENTLG: -24.76501 1bty.LigDockFin000.002.pdb:engPOTENTLG: -24.53164 1bty.LigDockFin000.003.pdb:engPOTENTLG: -24.44349 1bty.LigDockFin001.001.pdb:engPOTENTLG: -24.03668 1bty.LigDockFin001.002.pdb:engPOTENTLG: -22.61240 1bty.LigDockFin001.003.pdb:engPOTENTLG: -20.96410 1bty.LigDockFin002.001.pdb:engPOTENTLG: -40.25522 !best docking mode 1bty.LigDockFin002.002.pdb:engPOTENTLG: -40.24239 1bty.LigDockFin002.003.pdb:engPOTENTLG: -40.21294 1bty.LigDockFin003.001.pdb:engPOTENTLG: -13.18473 1bty.LigDockFin003.002.pdb:engPOTENTLG: -12.79959 1bty.LigDockFin003.003.pdb:engPOTENTLG: -12.70576 1bty.LigDockFin004.001.pdb:engPOTENTLG: -24.15409 1bty.LigDockFin004.002.pdb:engPOTENTLG: -23.90785 1bty.LigDockFin004.003.pdb:engPOTENTLG: -23.87370 1bty.LigDockFin005.001.pdb:engPOTENTLG: -28.31307 1bty.LigDockFin005.002.pdb:engPOTENTLG: -28.17037 1bty.LigDockFin005.003.pdb:engPOTENTLG: -28.14446 1bty.LigDockFin006.001.pdb:engPOTENTLG: -20.06244 1bty.LigDockFin006.002.pdb:engPOTENTLG: -18.94587 1bty.LigDockFin006.003.pdb:engPOTENTLG: -18.48825 1bty.LigDockFin007.001.pdb:engPOTENTLG: -18.42872 1bty.LigDockFin007.002.pdb:engPOTENTLG: -18.37239 ..... 1bty.LigDockFin013.001.pdb:engPOTENTLG: -21.23134 1bty.LigDockFin013.002.pdb:engPOTENTLG: -20.48702 1bty.LigDockFin013.003.pdb:engPOTENTLG: -19.79687 1bty.LigDockFin014.001.pdb:engPOTENTLG: -17.41916 1bty.LigDockFin014.002.pdb:engPOTENTLG: -17.05084 1bty.LigDockFin014.003.pdb:engPOTENTLG: -16.60287 1bty.LigDockFin015.001.pdb:engPOTENTLG: -21.14995 1bty.LigDockFin015.002.pdb:engPOTENTLG: -20.88982 1bty.LigDockFin015.003.pdb:engPOTENTLG: -20.61083 # **************************************************************** # # DOCK TEST#2 alpha-thrombin/bemzamidine complex : 1dwb # 1dwb.ben.Native.pdb 1dwb.ben.notNative.pdb - two variants of inPDB file # MdynPar_1dwb.inp moveRes_1dwb.inp SAprotocol_1dwb.inp : input Job Protocol files # file 1dwb.LigDockFin.ePL.res: - total potential energy of Lig-Lig + Lig-Prot interactions: # 1dwb.LigDockFin000.001.pdb:engPOTENTLG: -19.92194 1dwb.LigDockFin000.002.pdb:engPOTENTLG: -19.81434 1dwb.LigDockFin000.003.pdb:engPOTENTLG: -19.30406 1dwb.LigDockFin001.001.pdb:engPOTENTLG: -43.80969 !best docking mode 1dwb.LigDockFin001.002.pdb:engPOTENTLG: -43.79070 1dwb.LigDockFin001.003.pdb:engPOTENTLG: -43.69997 1dwb.LigDockFin002.001.pdb:engPOTENTLG: -21.91559 1dwb.LigDockFin002.002.pdb:engPOTENTLG: -18.90804 1dwb.LigDockFin002.003.pdb:engPOTENTLG: -18.59642 1dwb.LigDockFin003.001.pdb:engPOTENTLG: -30.16282 1dwb.LigDockFin003.002.pdb:engPOTENTLG: -25.75561 1dwb.LigDockFin003.003.pdb:engPOTENTLG: -25.32805 .. *************************************************************************************** #DOCK TEST#3 ./1dwc - alpha-Thrombin/MIT ligand complex # inPDB file: Job protocol files: MdynPar_1dwc_d2.inp moveRes_1dwc.inp SAprotocol_1dwc_03.inp # Docking result potential energy file: 1dwc.ePL.LigDockFin.res: # LigDockFin000.001.pdb:engPOTENTLG: -53.51793 !refined Native Binding mode LigDockFin000.002.pdb:engPOTENTLG: -52.98364 LigDockFin000.003.pdb:engPOTENTLG: -45.18925 LigDockFin001.001.pdb:engPOTENTLG: -50.56367 !best2 docking result = native mode (differenr Lig conformation) LigDockFin001.002.pdb:engPOTENTLG: -49.67875 LigDockFin001.003.pdb:engPOTENTLG: -47.75756 LigDockFin002.001.pdb:engPOTENTLG: -29.34865 LigDockFin002.002.pdb:engPOTENTLG: -28.29562 LigDockFin002.003.pdb:engPOTENTLG: -27.49329 LigDockFin003.001.pdb:engPOTENTLG: 158.53473 LigDockFin003.002.pdb:engPOTENTLG: 180.83168 LigDockFin003.003.pdb:engPOTENTLG: 214.47627 LigDockFin004.001.pdb:engPOTENTLG: -35.89280 LigDockFin004.002.pdb:engPOTENTLG: -33.39799 LigDockFin004.003.pdb:engPOTENTLG: -32.96119 ... LigDockFin029.001.pdb:engPOTENTLG: -25.19725 LigDockFin029.002.pdb:engPOTENTLG: -21.06659 LigDockFin029.003.pdb:engPOTENTLG: -18.58114 LigDockFin030.001.pdb:engPOTENTLG: -52.92000 !best1 docking mode = native mode LigDockFin030.002.pdb:engPOTENTLG: -45.43426 LigDockFin030.003.pdb:engPOTENTLG: -41.80339 ... **************************************************************************************** # DOCK TEST#4 ./1stp : complex streptavidine/biotin # inPDB files: 1stp.btn.notNative.pdb 1stp.btn.Native.pdb Job protocol files: MdynPar_1stp.inp moveRes_1stp.inp SAprotocol_1stp.inp # Docking result potential energy file: 1stp.LigDockFin.ePL.res # 1stp.LigDockFin000.001.pdb:engPOTENTLG: -20.67740 1stp.LigDockFin000.002.pdb:engPOTENTLG: -18.70130 1stp.LigDockFin000.003.pdb:engPOTENTLG: -16.49737 1stp.LigDockFin001.001.pdb:engPOTENTLG: -59.33578 !best docking MODE = native 1stp.LigDockFin001.002.pdb:engPOTENTLG: -58.89420 1stp.LigDockFin001.003.pdb:engPOTENTLG: -58.77360 1stp.LigDockFin002.001.pdb:engPOTENTLG: -24.83950 1stp.LigDockFin002.002.pdb:engPOTENTLG: -20.99019 .. **************************************************************************************** # #DOCK TEST#5 ./3tpi : complex Trypsinogen/ILE-VAL dipeptide # inPDB file : 3tpi.IV.notNative.pdb Job protocol files: MdynPar_3tpi.inp moveRes_3tpi.inp SAprotocol_3tpi.inp # Docking result potential energy file: 1stp.LigDockFin.ePL.res: # LigDockFin000.001.pdb:engPOTENTLG: -75.41046 LigDockFin000.002.pdb:engPOTENTLG: -74.73651 LigDockFin000.003.pdb:engPOTENTLG: -73.62763 LigDockFin001.001.pdb:engPOTENTLG: -76.07257 !best docking mode = native LigDockFin001.002.pdb:engPOTENTLG: -75.64239 LigDockFin001.003.pdb:engPOTENTLG: -75.56549 LigDockFin002.001.pdb:engPOTENTLG: -39.38153 LigDockFin002.002.pdb:engPOTENTLG: -37.80946 LigDockFin002.003.pdb:engPOTENTLG: -37.19353 LigDockFin003.001.pdb:engPOTENTLG: -44.83166 LigDockFin003.002.pdb:engPOTENTLG: -44.66529 LigDockFin003.003.pdb:engPOTENTLG: -44.60099 LigDockFin004.001.pdb:engPOTENTLG: -74.91846 !best2 docking mode ~ native: VALine side chain change conformation LigDockFin004.002.pdb:engPOTENTLG: -74.83774 LigDockFin004.003.pdb:engPOTENTLG: -73.65620 LigDockFin005.001.pdb:engPOTENTLG: -35.99043 LigDockFin005.002.pdb:engPOTENTLG: -34.74246 LigDockFin005.003.pdb:engPOTENTLG: -34.45740 LigDockFin006.001.pdb:engPOTENTLG: -34.24403 LigDockFin006.002.pdb:engPOTENTLG: -33.57267 LigDockFin006.003.pdb:engPOTENTLG: -33.01848 LigDockFin007.001.pdb:engPOTENTLG: -36.43544 ... # **************************************************************************************** #DOCK TEST#6 ./1hvr - complex HIV-1 protease/XK263 ligand : 1hvr PdB code # inPDB file : 1hvr.NativeMode.pdb job protocol files: MdynPar_1hvr.inp moveRes_1hvr.inp SAprotocol_1hvr.in # Docking result potential energy file: 1hvr.ePL.LigDockFin.res: LigDockFin000.001.pdb:engPOTENTLG: -72.49685 ! md optimized native binding mode LigDockFin000.002.pdb:engPOTENTLG: -67.88530 LigDockFin000.003.pdb:engPOTENTLG: -67.32499 LigDockFin001.001.pdb:engPOTENTLG: -75.05936 !** best1 docking mode = native LigDockFin001.002.pdb:engPOTENTLG: -74.41620 LigDockFin001.003.pdb:engPOTENTLG: -72.38953 LigDockFin002.001.pdb:engPOTENTLG: -27.65386 LigDockFin002.002.pdb:engPOTENTLG: -24.26098 LigDockFin002.003.pdb:engPOTENTLG: -23.37482 LigDockFin003.001.pdb:engPOTENTLG: -40.34463 LigDockFin003.002.pdb:engPOTENTLG: -35.47597 LigDockFin003.003.pdb:engPOTENTLG: -34.07937 ... LigDockFin008.001.pdb:engPOTENTLG: -15.30777 LigDockFin008.002.pdb:engPOTENTLG: -10.51002 LigDockFin008.003.pdb:engPOTENTLG: -3.76347 LigDockFin009.001.pdb:engPOTENTLG: -64.55802 !best2 docking mode = native like LigDockFin009.002.pdb:engPOTENTLG: -64.05453 LigDockFin009.003.pdb:engPOTENTLG: -36.51418 LigDockFin010.001.pdb:engPOTENTLG: -18.38447 ... # ************************************************************************************* # #DOCK TEST#7 ./4phv Complex HIV-1 protease with inhibitor VAC : PDB code 4phv # inPDB file: 4phv.NativeMode.pdb job protocol files: MdynPar_4phv.inp moveRes_4phv.inp SAprotocol_4phv.inp # Docking result potential energy file: 4phv.ePL.LigDockFin.res: # LigDockFin000.001.pdb:engPOTENTLG: -103.07942 !optimized NAtive binding mode LigDockFin000.002.pdb:engPOTENTLG: -102.91592 LigDockFin000.003.pdb:engPOTENTLG: -87.68965 LigDockFin001.001.pdb:engPOTENTLG: -96.85534 !best1 docking mode ~= native LigDockFin001.002.pdb:engPOTENTLG: -86.03489 LigDockFin001.003.pdb:engPOTENTLG: -72.52062 LigDockFin002.001.pdb:engPOTENTLG: -73.35270 !best2 docking mode : perturbed Lig conf. LigDockFin002.002.pdb:engPOTENTLG: -73.13903 LigDockFin002.003.pdb:engPOTENTLG: -72.76502 LigDockFin003.001.pdb:engPOTENTLG: -57.68087 LigDockFin003.002.pdb:engPOTENTLG: -57.64718 LigDockFin003.003.pdb:engPOTENTLG: -57.60190 ... # ********************************************************************************************** #DOCK TEST#8 ./1hiv Complex HIV-1 protease with inhibitor NOA Ligand (119 atoms): PDB code 1hiv # inPDB file : 1hiv.PL.NativeMode.pdb (ligand: 1hiv.Lig.NativeMode.pdb) # job protocol files: MdynPar_1hiv.inp moveRes_1hiv.inp SAprotocol_1hiv.inp # Docking result potential energy file: 1hiv.ePL.DockFin.res: LigDockFin000.001.pdb:engPOTENTLG: -69.74858 !native mode LigDockFin000.002.pdb:engPOTENTLG: -56.87684 LigDockFin000.003.pdb:engPOTENTLG: -49.21509 LigDockFin001.001.pdb:engPOTENTLG: -82.47626 !best1 docking mode: ~native with disturbed end groups of Lig LigDockFin001.002.pdb:engPOTENTLG: -75.56277 LigDockFin001.003.pdb:engPOTENTLG: -58.60314 LigDockFin002.001.pdb:engPOTENTLG: -68.50492 !best2 docking mode: ~native with disturbed end groups of Lig LigDockFin002.002.pdb:engPOTENTLG: -46.25002 LigDockFin002.003.pdb:engPOTENTLG: -46.19144 LigDockFin003.001.pdb:engPOTENTLG: -18.98590 .... LigDockFin011.003.pdb:engPOTENTLG: -9.30396 LigDockFin012.001.pdb:engPOTENTLG: -59.47753 !best3 docking mode LigDockFin012.002.pdb:engPOTENTLG: -59.12785 LigDockFin012.003.pdb:engPOTENTLG: -55.48428 .... ******************************************************************************************** RESUME : 1) all shown test example of docking module successevely find a set of docking modes, i.e. files LigDockFinXXX.XXX.pdb 2) the mode with minimal potential energy of Protein-Lig interactions in the set of files LigDockFinXXX.XXX.pdb are the mode closeto the rective native ligand structure in the complex. The RMSD of the best docking mode from the native are withng 1 - 2 A. 3) The current docking method does not guarantee a finding of the best docking solution in the one RUN. The best docking solution can be obtained by refinement of the best (in the first run) docking solutions. *********************************************************************************************