MolDyn - Instalation and RUN
MolDyn - Instalation and RUN
#
mDyn - molecular dynamics program
Purpose of program
1) relaxation of a molecular 3D structure via optimization of molecular conformational
energy via local optimization methods
2) pseudo-global relaxation of conformational energy via simulation of thermal fluctuations
of atoms via method of molecular dynamics in an explicit or implicit solvent using
user defined positional or atom-atom distance restraints.
3) simulation of equilibrium molecular dynamics of protein
4) BLIND DOCKING OF FLEXIBLE LIGAND :
a) calculation of low-resolution binding sites
b) docking for user defined initial site of Protein
c) automatic blind docking of Ligand on Protein via hierarchical method including
refinement of ligand position/orientation and conformation via molecular dynamic
simulated annealing coupled with force field deformation of ligand-protein interactions
#
USE of program
1)DOS installation
make dir myMdynQ09/
put program mMdynQ09.exe to this directory
subDirectories myMdynQ09/dat have to contain all file.dat - Lib data for program
myMdynQ09/src fortran code files
MAKE enviromenr variable
> set MDYN09HOME="fullPath to myMdyn09/dat"
myMdynQ09/doc directory contains Mannual and *.txt files
explaining how to run program and undestand results of calculations
RUN program from separate /jobX directory
2) Linux installation
a) copy mDynQ09.tgz to myMdyn09/ directory
b) extract archive
> tar -zxvf mDynQ09.tgz
c) set env variable $MDYN09HOMED
> . ./setMDynQ09.sh
3) Compilation
cd to source dir $MDYN09HOME/src
do commands:
g77 -c -O3 *.f
g77 *.o -O3 -o mDynQ09
#- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
4) RUN program by the command
../$MDYN09HOME/mDynQ09 -i inProtcol -c inPDB [-cL 1etr.L.h.0.pdb] [-mdR mdRestXYZVin] [-mv moveRes]
[-r1 inRestrainA1 ] [-r2 inRestrainA2] [-rB rigBodyFile]
[-sa saProtocol] [-mn molName] [-mdX mdFinalPDB]
[-tL ligMolTopoDat] [-bsX bsXYZinPDBfile] -o runOutFile [-er errorFile]
in parenthesis [ ] are uxilarry files. The auxilary files will be used by program if the main command file
defines the 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
-cL 1etr.L.h.0.pdb - Ligand allAtom structure
-tL ligMolTopoDat : file of LigandMolecTopology created by program mTopoHQ
-bsX bsXYZinPDBfile: file of low-resolution binding site positions to be refined
-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 needs an additional 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
#
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# INPUT file description
#
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
! by default OUTshort option is ON
#Initial PDB data quality
$Hread ! read INPUT pdb file with Hydrogens
# 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
$shake=1 ! all H-X bonds are fixed
! default shake=0, all bonds are flexible, RECOMENDED
#
$zeroRot ! exclude translation and rotation of the molecule
as rigid body
$hBond128 = 2.0 ! scaling coeff for H-bonds
! default=1.0 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 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
----------------------------------------------------
#Definition 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 < R2=14 A
REMARK: restr1Eng: 2.37470 <- atomA1positional restrain eng
REMARK: eRstA2Eng: 137.93436 <- atom-atom distances restrain eng
REMARK: eCompcEng: 3.04940 <- artificial compactization energy
REMARK: eGeoDef : 1269.46936 <- total ValenceGeometryDeformation eng
REMARK: engCOUL : -820.72534 <- total COIUL eng
REMARK: engSolvGS: -311.56546 <- GaussianShell solvation model eng
REMARK: engSolHP : 0.00000 <- Hydrophocic cavity solvation energy
REMARK: bornPolz : 0.00000 <- Generalized Born model polarization eng
REMARK: engSolWatBrg: 0.00000 <- Water Bridges solvation energy
REMARK: engSolTot: -311.56546 <-total solvation energy
REMARK: engPOTENT: -1502.68958 <- total potential energy
REMARK: kinEng : 517.13666 <- thermal kinetic energy
REMARK: Temp(K) : 87.45163 <- effective temperature (K) of atomic motions
REMARK: engTotal : -985.55292 <- total energy = Potential + Kinetic
REMARK:
REMARK: PDB: X Y Z Q atom
ATOM 1 N GLY A 1 11.289 -9.838 10.638 0.29430
ATOM 2 H1 GLY A 1 11.186 -10.306 9.749 0.16420
ATOM 3 H2 GLY A 1 12.210 -9.985 11.026 0.16420
etc.
TER
END
REMARK: GEOMETRY ANALYSYS:
REMARK: BAD BOND LIST:
REMARK: BAD BOND 1 C ARG 156 -N ILE 157 : 1.3990 err: 0.0640
REMARK: BAD ANGL LIST:
# ANGLE between atoms at1 at2 at3 angl(grad)
REMARK: BAD ANGLE 1 C GLY 1 -N VAL 2 -CA VAL 2 : 129.771 err: 8.071
REMARK: BAD ANGLE 2 N SER 5 -CA SER 5 -CB SER 5 : 102.698 err: -7.802
REMARK: BAD ANGLE 3 O SER 5 -C SER 5 -N CYX 6 : 115.473 err: -7.527
REMARK: BAD ANGLE 4 CB ILE 8 -CA ILE 8 -C ILE 8 : 122.456 err: 12.356
REMARK: BAD ANGLE 5 C ASP 9 -N VAL 10 -CA VAL 10 : 128.773 err: 7.073
etc.
REMARK: BAD ANGLE 51 C ASP 259 -N GLY 260 -CA GLY 260 : 128.458 err: 6.758
REMARK: END