bfee2 3.1.1.post1__py3-none-any.whl

BFEE2/templates_namd/configTemplate.py

@@ -0,0 +1,1152 @@
+# generate NAMD/Gromacs/Colvars config files
+
+import numpy as np
+
+class configTemplate:
+    ''' generate NAMD/Gromacs/Colvars config files
+        In the Colvars config file, ndx and xyz files are used to indicate the group of atoms
+        The non-hydrogen atoms of protein are labeled as 'protein' in complex.ndx
+        The non-hydrogen atoms of ligand are labeled as 'ligand' in complex.ndx
+        The non-hydrogen atoms of user-defined reference are labeled as 'reference' in complex.ndx '''
+
+    def __init__(self):
+        pass
+
+    def namdConfigTemplate(
+                            self,
+                            forceFieldType,
+                            forceFieldFiles,
+                            topFile,
+                            coorFile,
+                            NAMDRestartCoor,
+                            NAMDRestartVel,
+                            NAMDRestartXsc,
+                            PBCCondition,
+                            outputPrefix,
+                            temperature,
+                            numSteps,
+                            cvFile = '',
+                            cvDefinitionFile = '',
+                            CVRestartFile = '',
+                            fepFile = '',
+                            fepWindowNum = 20,
+                            fepForward = True,
+                            fepDoubleWide = False,
+                            fepMinBeforeSample = False,
+                            membraneProtein = False,
+                            OPLSMixingRule = False,
+                            GaWTM = False,
+                            CUDASOAIntegrator = False,
+                            timestep = 2.0,
+                            LDDMStep1 = False,
+                            lambdaABF = False
+                            ):
+        """the namd config file template
+
+        Args:
+            forceFieldType (str): 'charmm' or 'amber'
+            forceFieldFiles (list of str): name of charmm force field files
+            topFile (str): name of the topology file (psf, parm) 
+            coorFile (str): name of the coordinate file (pdb, rst)
+            NAMDRestartCoor (str): name of namd binary restart coor file (if restart from a previous simulation)
+            NAMDRestartVel (str): name of namd binary restart vel file
+            NAMDRestartXsc (str): name of namd restart xsc file
+            PBCCondition (np.array, 2*3): PBC vector, ((lengthX, lengthY, lengthZ),(centerX, centerY, centerZ))
+            outputPrefix (str): prefix of output file
+            temperature (float): temperature of the simulation
+            numSteps (int): number of steps of the simulation
+            cvFile (str): name of Colvars file. Defaults to ''.
+            cvDefinitionFile (str, optional): name of a TCL file defining new CVs. Defaults to ''.
+            CVRestartFile (str, optional): name of Colvars restart file. Defaults to ''.
+            fepFile (str, optional): name of fep file, indicating which atoms will be generated/removed 
+                                     (if run alchemical simulation). Defaults to ''.
+            fepWindowNum (int, optional): number of fep windows. Defaults to 20.
+            fepForward (bool, optional): whether this is a forward fep simulation. Defaults to True.
+            fepDoubleWide (bool, optional): whether this is a double-wide fep simulation. Defaults to False.
+            fepMinBeforeSample (bool, optional): whether do minimization before sampling in each FEP window.
+                                                 Defaults to False.
+            membraneProtein (bool, optional): whether simulating a membrame protein. Defaults to False.
+            OPLSMixingRule (bool, optional): whether use the OPLS mixing rules. Defaults to False.
+            GaWTM (bool, optional): Whether this is an GaWTM-eABF simulation. Default to False
+            CUDASOAIntegrator (bool, optional): Whether CUDASOA integrator is used. Default to False
+            timestep (float, optional): timestep of the simulation. Default to 2.0
+            LDDMStep1 (bool, optional): whether this is the 1st step of a LDDM simulation. Default to False.
+            lambdaABF (bool, optional): whether use WTM-lambdaABF. This option is incompatible with FEP. Default to False.
+
+        Returns:
+            str: a NAMD config string if succeed, and empty string otherwise
+        """
+
+        assert(forceFieldType == 'charmm' or forceFieldType == 'amber')
+        assert(not lambdaABF or cvFile != '')
+        assert(not lambdaABF or fepFile != '')
+
+        configString = f'\
+coordinates    {coorFile}                   \n'
+
+        # force field files
+        if forceFieldType == 'charmm':
+            configString += f'\
+structure      {topFile}                \n\
+paraTypeCharmm    on                    \n'
+            for ff in forceFieldFiles:
+                configString += f'\
+parameters    {ff}                      \n'
+        elif forceFieldType == 'amber':
+            configString += f'\
+parmFile      {topFile}                 \n\
+amber    on                             \n'
+        else:
+            # error
+            return ''
+
+        # structure
+        if forceFieldType == 'charmm':
+            configString += f'\
+exclude    scaled1-4                    \n\
+1-4scaling    1.0                       \n\
+switching            on                 \n\
+switchdist           10.0               \n\
+cutoff               12.0               \n\
+pairlistdist         14.0               \n'
+        elif forceFieldType == 'amber':
+            configString += f'\
+exclude    scaled1-4                    \n\
+1-4scaling    0.83333333                \n\
+switching            on                 \n\
+switchdist           9.0                \n\
+cutoff               10.0               \n\
+pairlistdist         12.0               \n'
+        else:
+            # error
+            return ''
+        
+        # OPLS mixing rule
+        if OPLSMixingRule:
+            configString += f'\
+vdwGeometricSigma    yes               \n'
+
+        if NAMDRestartCoor == '' and NAMDRestartVel == '' and NAMDRestartXsc == '' and isinstance(PBCCondition, np.ndarray):
+            # set temperature
+            configString += f'\
+temperature    {temperature}                      \n\
+cellBasisVector1    {PBCCondition[0][0]} 0 0         \n\
+cellBasisVector2    0 {PBCCondition[0][1]} 0         \n\
+cellBasisVector3    0 0 {PBCCondition[0][2]}         \n\
+cellOrigin    {PBCCondition[1][0]} {PBCCondition[1][1]} {PBCCondition[1][2]}  \n'
+        elif NAMDRestartCoor != '' and NAMDRestartVel != '' and NAMDRestartXsc != '' and PBCCondition == '':
+            # restart from files
+            configString += f'\
+bincoordinates    {NAMDRestartCoor}                          \n\
+binvelocities    {NAMDRestartVel}                            \n\
+ExtendedSystem    {NAMDRestartXsc}                           \n'
+        else:
+            # error
+            return ''
+        
+        if lambdaABF:
+            configString += f'\
+computeEnergies      1                          \n'   # required by WTM-lambda ABF
+
+        # other parameters
+        configString += f'\
+binaryoutput         yes                        \n\
+binaryrestart        yes                        \n\
+outputname           {outputPrefix}             \n\
+dcdUnitCell          yes                        \n\
+outputenergies       5000                       \n\
+outputtiming         5000                       \n\
+outputpressure       5000                       \n\
+restartfreq          5000                       \n\
+XSTFreq              5000                       \n\
+dcdFreq              5000                       \n\
+hgroupcutoff         2.8                        \n\
+wrapAll              off                        \n\
+wrapWater            on                         \n\
+langevin             on                         \n\
+langevinDamping      1                          \n\
+langevinTemp         {temperature}              \n\
+langevinHydrogen     no                         \n\
+langevinpiston       on                         \n\
+langevinpistontarget 1.01325                    \n\
+langevinpistonperiod 200                        \n\
+langevinpistondecay  100                        \n\
+langevinpistontemp   {temperature}              \n\
+usegrouppressure     yes                        \n\
+PME                  yes                        \n\
+PMETolerance         10e-6                      \n\
+PMEInterpOrder       4                          \n\
+PMEGridSpacing       1.0                        \n\
+timestep             {timestep}                 \n\
+fullelectfrequency   2                          \n\
+nonbondedfreq        1                          \n\
+rigidbonds           all                        \n\
+rigidtolerance       0.00001                    \n\
+rigiditerations      400                        \n\
+stepspercycle        10                         \n\
+splitpatch           hydrogen                   \n\
+margin               2                          \n'
+
+        # membrane protein
+        if membraneProtein:
+            configString += f'\
+useflexiblecell      yes                        \n\
+useConstantRatio     yes                        \n'
+        else:
+            configString += f'\
+useflexiblecell      no                         \n\
+useConstantRatio     no                         \n'
+            
+        # CUDASOA integrator
+        if CUDASOAIntegrator:
+            configString += f'\
+CUDASOAIntegrate     on                         \n'
+
+        # colvars definition
+        if cvFile != '':
+            configString += f'\
+colvars    on                                   \n'
+            if not GaWTM:
+                configString += f'\
+colvarsConfig    {cvFile}                       \n'
+
+                if CVRestartFile != '':
+                    configString += f'\
+colvarsInput     {CVRestartFile}                \n'
+
+
+        if cvDefinitionFile != '':
+            configString += f'\
+source     {cvDefinitionFile}                   \n'
+
+        # fep
+        if fepFile == '' and (not lambdaABF):
+            if NAMDRestartCoor == '' and NAMDRestartVel == '' and NAMDRestartXsc == '':
+                configString += f'\
+minimize    500                                 \n\
+reinitvels    {temperature}                     \n'
+            if not GaWTM:
+                configString += f'\
+run    {numSteps}                               \n'
+            else:
+                configString += f'\
+accelMD                         on                     \n\
+accelMDG                        on                     \n\
+accelMDdihe                     on                     \n\
+accelMDOutFreq                  1000                   \n\
+accelMDGSigma0D                 6.0                    \n'
+                if CVRestartFile == '':
+                     # new GaMD-WTM-eABF simulation
+                     configString += f'\
+accelMDGcMDSteps                500000                 \n\
+accelMDGcMDPrepSteps            100000                 \n\
+accelMDGEquiPrepSteps           100000                 \n\
+accelMDGEquiSteps               500000                 \n\
+for {{set stage 0}} {{$stage < 2}} {{incr stage}} {{   \n\
+    if {{$stage == 0}} {{                              \n\
+        puts "Probing the GaMD parameters..."          \n\
+        cv configfile {cvFile}                         \n\
+        run norepeat 1000000                           \n\
+    }} elseif {{$stage == 1}} {{                       \n\
+        puts "Starting eABF + GaMD..."                 \n\
+        cv reset                                       \n\
+        cv configfile {cvFile + ".amd"}                \n\
+        run norepeat   {numSteps}                      \n\
+    }}                                                 \n\
+}}                                                     \n'
+                else:
+                     configString += f'\
+accelMDGcMDSteps                0                      \n\
+accelMDGcMDPrepSteps            0                      \n\
+accelMDGEquiPrepSteps           0                      \n\
+accelMDGEquiSteps               0                      \n\
+accelMDGRestart                 on                     \n\
+accelMDGRestartFile             {CVRestartFile}.gamd   \n\
+colvarsConfig                   {cvFile + ".amd"}      \n\
+colvarsInput                    {CVRestartFile}        \n\
+run norepeat   {numSteps}                              \n'
+
+        elif fepFile != '' and (not lambdaABF):
+            # currently the alchemical route is somewhat hard-coded
+            # this will be improved in the future
+            if LDDMStep1:
+                configString += f'\
+source ./fep_lddm.tcl                           \n'
+            else:
+                configString += f'\
+source ../fep.tcl                               \n'  
+            configString += f'\
+alch on                                         \n\
+alchType FEP                                    \n\
+alchFile {fepFile}                              \n\
+alchCol B                                       \n\
+alchOutFile {outputPrefix}.fepout               \n\
+alchOutFreq 50                                  \n\
+alchVdwLambdaEnd 0.7                            \n\
+alchElecLambdaStart 0.5                         \n\
+alchDecouple   on                               \n\
+alchEquilSteps 100000                           \n'
+
+            if fepForward:
+                if not fepDoubleWide:
+                    if fepMinBeforeSample:
+                        # minimize before sampling
+                        configString += f'\
+runFEPmin 0.0 1.0 {1.0/fepWindowNum} 500000 1000 {temperature}\n'
+                    else:
+                        configString += f'\
+runFEP 0.0 1.0 {1.0/fepWindowNum} 500000\n'
+
+                else:
+                    # double wide simulation
+                    configString += f'\
+runFEP 0.0 1.0 {1.0/fepWindowNum} 500000 true\n'
+
+            else:
+                # backward
+                if not fepDoubleWide:
+                    if fepMinBeforeSample:
+                        # minimize before sampling
+                        configString += f'\
+runFEPmin 1.0 0.0 {-1.0/fepWindowNum} 500000 1000 {temperature}\n'
+                    else:
+                        configString += f'\
+runFEP 1.0 0.0 {-1.0/fepWindowNum} 500000\n'
+
+                else:
+                    # double wide simulation
+                    configString += f'\
+runFEP 1.0 0.0 {-1.0/fepWindowNum} 500000 true\n'
+        
+        else:
+            # lambda ABF instead of FEP
+            configString += f'\
+alch on                                         \n\
+alchType TI                                     \n\
+alchFile {fepFile}                              \n\
+alchCol B                                       \n\
+alchOutFile {outputPrefix}.fepout               \n\
+alchOutFreq 5000                                \n\
+alchVdwLambdaEnd 0.7                            \n\
+alchElecLambdaStart 0.5                         \n\
+alchDecouple   on                               \n\
+alchlambda     0                                \n\
+run    {numSteps}                               \n'
+
+        return configString
+    
+    def gromacsMinimizeConfigTemplate(self):
+        """the gromacs config file template for minimization
+        
+        Returns:
+            str: a Gromacs config string if succeed, and empty string otherwise
+        """
+        configString = f'\
+integrator      = steep     \n\
+emtol           = 418.4     \n\
+emstep          = 0.01      \n\
+nsteps          = 20000     \n\
+nstlist         = 1         \n\
+cutoff-scheme   = Verlet    \n\
+ns_type         =           \n\
+coulombtype     = PME       \n\
+rcoulomb        = 1.2       \n\
+rvdw            = 1.2       \n\
+pbc             = xyz       \n'
+        return configString
+    
+    def gromacsConfigTemplate(
+                            self,
+                            forceFieldType,
+                            temperature,
+                            numSteps,
+                            membraneProtein = False,
+                            generateVelocities = True
+                            ):
+        """the gromacs config file template
+
+        Args:
+            forceFieldType (str): 'charmm' or 'amber'
+            temperature (float): temperature of the simulation
+            numSteps (int): number of steps of the simulation
+            membraneProtein (bool, optional): whether simulating a membrame protein. Defaults to False.
+            generateVelocities (bool, optional): whether generate velocities. Defaults to True.
+            
+        Returns:
+            str: a Gromacs config string if succeed, and empty string otherwise
+        """
+        
+        configString = f'\
+integrator              = md                \n\
+nsteps                  = {numSteps}        \n\
+dt                      = 0.002             \n\
+nstxout                 = 5000              \n\
+nstvout                 = 5000              \n\
+nstenergy               = 5000              \n\
+nstlog                  = 5000              \n\
+continuation            = no                \n\
+constraint_algorithm    = lincs             \n\
+constraints             = h-bonds           \n\
+cutoff-scheme           = Verlet            \n\
+nstlist                 = 10                \n\
+coulombtype             = PME               \n'
+
+        if forceFieldType == 'charmm':
+            configString += f'\
+rcoulomb                = 1.2               \n\
+rvdw                    = 1.2               \n\
+rvdw-switch             = 1.0               \n'
+
+        elif forceFieldType == 'amber':
+            configString += f'\
+rcoulomb                = 0.9               \n\
+rvdw                    = 0.9               \n\
+rvdw-switch             = 0.8               \n'
+
+        configString += f'\
+vdwtype                 = Cut-off                \n\
+vdw-modifier            = force-switch           \n\
+DispCorr                = EnerPres               \n\
+tcoupl                  = V-rescale              \n\
+tc-grps                 = System                 \n\
+tau_t                   = 1                      \n\
+ref_t                   = {temperature}          \n\
+pbc                     = xyz                    \n\
+pcoupl                  = C-rescale              \n\
+tau-p                   = 1                      \n'
+
+        if not membraneProtein:
+            configString += f'\
+ref-p                   = 1.01325                \n\
+compressibility         = 4.5e-5                 \n\
+refcoord-scaling        = com                    \n\
+pcoupltype              = isotropic              \n'
+
+        elif membraneProtein:
+            configString += f'\
+ref-p                   = 1.01325 1.01325        \n\
+compressibility         = 4.5e-5 4.5e-5          \n\
+refcoord-scaling        = com                    \n\
+pcoupltype              = semiisotropic          \n'
+    
+        if generateVelocities:
+            configString += f'\
+gen_vel                 = yes                    \n\
+gen_temp                = {temperature}          \n\
+gen_seed                = -1                     \n'
+
+        return configString
+    
+    def cvLambdaTemplate(self, bins):
+        """lambda CV template for WTM-lambdaABF
+
+        Args:
+            bins (int): number of bins for the CV
+
+        Returns:
+            str: string of lambda definition
+        """
+        string = f'\
+colvar {{                                \n\
+    name l                               \n\
+    extendedLagrangian on                \n\
+    extendedMass 150000                  \n\
+    extendedLangevinDamping 1000         \n\
+    lowerBoundary 0                      \n\
+    upperBoundary 1                      \n\
+    reflectingLowerBoundary              \n\
+    reflectingUpperBoundary              \n\
+    width {1/float(bins)}                \n\
+    subtractAppliedForce                 \n\
+    expandboundaries                     \n\
+    alchLambda {{                        \n\
+    }}                                   \n\
+    outputTotalForce                     \n\
+    outputAppliedforce                   \n\
+}}                                       \n'
+        return string
+
+    def cvRMSDTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, refFile, 
+            extendedLagrangian = True, reflectingBoundary = False,
+            unit = 'namd'
+        ):
+        """RMSD CV template
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperboundary (float): upper boundary of free-energy calculation
+            refFile (str): path to the reference file
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+            unit (str, optional): unit, 'namd' or 'gromacs'. Default to namd.
+        
+        Returns:
+            str: string of RMSD definition
+        """
+        
+        if unit == 'namd':
+            scaleFactor = 1
+        elif unit == 'gromacs':
+            scaleFactor = 0.1
+
+        string = f'\
+colvar {{                                    \n\
+    name RMSD                                \n'
+
+        if setBoundary:
+            string += f'\
+    width {0.05 * scaleFactor:.2f}                               \n\
+    lowerboundary {lowerBoundary * scaleFactor:.2f}            \n\
+    upperboundary {upperBoundary * scaleFactor:.2f}            \n'
+    
+        if setBoundary and reflectingBoundary:
+            string += f'\
+    reflectingLowerboundary  on              \n\
+    reflectingUpperboundary  on              \n'
+    
+        if extendedLagrangian:
+            string += f'\
+    subtractAppliedForce on                  \n\
+    expandboundaries  on                     \n\
+    extendedLagrangian on                    \n\
+    extendedFluctuation {0.05 * scaleFactor:.2f}                 \n'
+
+        string += f'\
+    rmsd {{                                  \n\
+        atoms {{                             \n\
+            indexGroup  ligand               \n\
+        }}                                   \n\
+        refpositionsfile  {refFile}          \n\
+    }}                                       \n\
+}}                                           \n'
+        return string
+    
+    def cvAngleTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, angle, 
+            refFile, oldDefinition = True, extendedLagrangian = True, reflectingBoundary = False
+        ):
+        """Eulaer and polar angle template
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperBoundary (float): upper boundary of free-energy calculation
+            angle (str): 'eulerTheta', 'eulerPhi', 'eulerPsi', 'polarTheta' or 'polarPhi'
+            refFile (str): path to the reference file
+            oldDefinition (bool, optional): Whether use old definition of angles
+                                            for compatibility. Defaults to True
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+        """
+        
+        assert(
+            angle == 'eulerTheta' or angle == 'eulerPhi' or angle == 'eulerPsi' or \
+            angle == 'polarTheta' or angle == 'polarPhi'
+        )
+        
+        if angle == 'eulerTheta' or angle == 'eulerPhi' or angle == 'eulerPsi':
+            if oldDefinition:
+                return self.cvEulerAngleTemplate(
+                           setBoundary, lowerBoundary, upperBoundary, angle, refFile, extendedLagrangian, reflectingBoundary
+                       )
+            else:
+                return self.newCvEulerAngleTemplate(
+                           setBoundary, lowerBoundary, upperBoundary, angle, refFile, extendedLagrangian, reflectingBoundary
+                       )
+        elif angle == 'polarTheta' or angle == 'polarPhi':
+            if oldDefinition:
+                return self.cvPolarAngleTemplate(
+                           setBoundary, lowerBoundary, upperBoundary, angle, refFile, extendedLagrangian, reflectingBoundary
+                       )
+            else:
+                return self.newCvPolarAngleTemplate(
+                           setBoundary, lowerBoundary, upperBoundary, angle, refFile, extendedLagrangian, reflectingBoundary
+                       )
+
+    def cvEulerAngleTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, angle, 
+            refFile, extendedLagrangian = True, reflectingBoundary = False
+        ):
+        """Euler angle template
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperboundary (float): upper boundary of free-energy calculation
+            angle (str): 'eulerTheta', 'eulerPhi' or 'eulerPsi'
+            refFile (str): path to the reference file
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+            
+        Returns:
+            string: string of Euler angle definition
+        """
+
+        assert(angle == 'eulerTheta' or angle == 'eulerPhi' or angle == 'eulerPsi')
+        
+        string = f'\
+colvar {{                              \n\
+    name {angle}                   \n'
+
+        if angle == 'eulerTheta':
+            string += f'\
+    customFunction asin(2 * (q1*q3-q4*q2)) * 180 / 3.1415926\n'
+        elif angle == 'eulerPhi':
+            string += f'\
+    customFunction atan2(2*(q1*q2+q3*q4), 1-2*(q2*q2+q3*q3)) * 180 / 3.1415926\n'
+        elif angle == 'eulerPsi':
+            string += f'\
+    customFunction atan2(2*(q1*q4+q2*q3), 1-2*(q3*q3+q4*q4)) * 180 / 3.1415926\n'
+
+        if setBoundary:
+            string += f'\
+    width 1                            \n\
+    lowerboundary {lowerBoundary:.1f}      \n\
+    upperboundary {upperBoundary:.1f}      \n'
+    
+        if setBoundary and reflectingBoundary:
+            string += f'\
+    reflectingLowerboundary  on              \n\
+    reflectingUpperboundary  on              \n'
+        
+        if extendedLagrangian:
+            string += f'\
+    subtractAppliedForce on            \n\
+    expandboundaries  on               \n\
+    extendedLagrangian on              \n\
+    extendedFluctuation 1              \n'
+
+        string += f'\
+    Orientation {{                             \n\
+        name  q                                \n\
+        atoms {{                               \n\
+            indexGroup  ligand                 \n\
+            centerReference    on              \n\
+            rotateReference    on              \n\
+            fittingGroup {{                    \n\
+                indexGroup  protein            \n\
+            }}                                 \n\
+            refpositionsfile  {refFile}        \n\
+         }}                                    \n\
+         refpositionsfile  {refFile}           \n\
+    }}                                         \n\
+}}                                             \n'
+
+        return string
+
+    def cvPolarAngleTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, angle, 
+            refFile, extendedLagrangian = True, reflectingBoundary = False
+        ):
+        """Polar angle template
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperboundary (float): upper boundary of free-energy calculation
+            angle (str): 'polarTheta' or 'polarPhi'
+            refFile (str): path to the reference file
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+            
+        Return:
+            str: string of polar angle definition
+        """
+
+        assert(angle == 'polarTheta' or angle == 'polarPhi')
+        
+        string = f'\
+colvar {{                                   \n\
+    name {angle}                            \n'
+
+        if angle == 'polarTheta':
+            string += f'\
+    customFunction acos(-i2) * 180 / 3.1415926\n'
+        elif angle == 'polarPhi':
+            string += f'\
+    customFunction atan2(i3, i1) * 180 / 3.1415926\n\
+    period  360                             \n\
+    wrapAround 0.0                          \n'
+
+        if setBoundary:
+            string += f'\
+    width 1                                 \n\
+    lowerboundary {lowerBoundary:.1f}           \n\
+    upperboundary {upperBoundary:.1f}           \n'
+    
+        if setBoundary and reflectingBoundary:
+            string += f'\
+    reflectingLowerboundary  on              \n\
+    reflectingUpperboundary  on              \n'
+    
+        if extendedLagrangian:
+            string += f'\
+    subtractAppliedForce on                 \n\
+    expandboundaries  on                    \n\
+    extendedLagrangian on                   \n\
+    extendedFluctuation 1                   \n'
+
+        string += f'\
+    distanceDir {{                          \n\
+        name  i                             \n\
+        group1 {{                           \n\
+            indexGroup  reference           \n\
+            centerReference    on           \n\
+            rotateReference    on           \n\
+            fittingGroup {{                 \n\
+                indexGroup  reference       \n\
+            }}                              \n\
+            refpositionsfile  {refFile}     \n\
+        }}                                  \n\
+        group2 {{                           \n\
+            indexGroup  ligand              \n\
+            centerReference    on           \n\
+            rotateReference    on           \n\
+            fittingGroup {{                 \n\
+                indexGroup  reference       \n\
+            }}                              \n\
+            refpositionsfile  {refFile}     \n\
+        }}                                  \n\
+    }}                                      \n\
+}}                                          \n'
+        return string
+    
+    def newCvEulerAngleTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, angle, 
+            refFile, extendedLagrangian = True, reflectingBoundary = False
+        ):
+        """new definition Euler angle template, probably the pinning down the protein is not required
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperboundary (float): upper boundary of free-energy calculation
+            angle (str): 'eulerTheta', 'eulerPhi' of 'eulerPsi'
+            refFile (str): path to the reference file
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+            
+        Returns:
+            string: string of Euler angle definition
+        """
+
+        assert(angle == 'eulerTheta' or angle == 'eulerPhi' or angle == 'eulerPsi')
+        
+        string = f'\
+colvar {{                              \n\
+    name {angle}                   \n'
+
+        if setBoundary:
+            string += f'\
+    width 1                            \n\
+    lowerboundary {lowerBoundary:.1f}      \n\
+    upperboundary {upperBoundary:.1f}      \n'
+    
+        if setBoundary and reflectingBoundary:
+            string += f'\
+    reflectingLowerboundary  on              \n\
+    reflectingUpperboundary  on              \n'
+        
+        if extendedLagrangian:
+            string += f'\
+    subtractAppliedForce on            \n\
+    expandboundaries  on               \n\
+    extendedLagrangian on              \n\
+    extendedFluctuation 1              \n'
+
+        string += f'\
+    {angle} {{                             \n\
+        atoms {{                               \n\
+            indexGroup  ligand                 \n\
+            centerReference    on              \n\
+            rotateReference    on              \n\
+            centerToOrigin     on              \n\
+            fittingGroup {{                    \n\
+                indexGroup  protein            \n\
+            }}                                 \n\
+            refpositionsfile  {refFile}        \n\
+         }}                                    \n\
+         refpositionsfile  {refFile}           \n\
+    }}                                         \n\
+}}                                             \n'
+
+        return string
+    
+    def newCvPolarAngleTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, angle, 
+            refFile, extendedLagrangian = True, reflectingBoundary = False
+        ):
+        """new definition of Polar angle template, probably the pinning down the protein is not required
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperboundary (float): upper boundary of free-energy calculation
+            angle (str): 'polarTheta' or 'polarPhi'
+            refFile (str): path to the reference file
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+            
+        Return:
+            str: string of polar angle definition
+        """
+
+        assert(angle == 'polarTheta' or angle == 'polarPhi')
+        
+        string = f'\
+colvar {{                                   \n\
+    name {angle}                            \n'
+    
+        if angle == 'polarTheta':
+            string += f'\
+    customFunction acos(-sin(t / 180 * 3.1415926) * sin(p / 180 * 3.1415926)) * 180 / 3.1415926\n'
+        elif angle == 'polarPhi':
+            string += f'\
+    customFunction atan2(cos(t / 180 * 3.1415926), cos(p / 180 * 3.1415926) * sin(t / 180 * 3.1415926)) * 180 / 3.1415926\n\
+    period  360                             \n\
+    wrapAround 0.0                          \n'
+
+        if setBoundary:
+            string += f'\
+    width 1                                 \n\
+    lowerboundary {lowerBoundary:.1f}           \n\
+    upperboundary {upperBoundary:.1f}           \n'
+    
+        if setBoundary and reflectingBoundary:
+            string += f'\
+    reflectingLowerboundary  on              \n\
+    reflectingUpperboundary  on              \n'
+        
+        if extendedLagrangian:
+            string += f'\
+    subtractAppliedForce on                 \n\
+    expandboundaries  on                    \n\
+    extendedLagrangian on                   \n\
+    extendedFluctuation 1                   \n'
+
+        string += f'\
+    polarTheta {{                             \n\
+        name        t                          \n\
+        atoms {{                               \n\
+            indexGroup  ligand                 \n\
+            centerReference    on              \n\
+            rotateReference    on              \n\
+            centerToOrigin     on              \n\
+            fittingGroup {{                    \n\
+                indexGroup  reference          \n\
+            }}                                 \n\
+            refpositionsfile  {refFile}        \n\
+         }}                                    \n\
+    }}                                         \n\
+    polarPhi {{                             \n\
+        name        p                      \n\
+        atoms {{                               \n\
+            indexGroup  ligand                 \n\
+            centerReference    on              \n\
+            rotateReference    on              \n\
+            centerToOrigin     on              \n\
+            fittingGroup {{                    \n\
+                indexGroup  reference          \n\
+            }}                                 \n\
+            refpositionsfile  {refFile}        \n\
+         }}                                    \n\
+    }}                                         \n\
+}}                                             \n'
+        return string
+
+    def cvRTemplate(
+            self, setBoundary, lowerBoundary, upperBoundary, 
+            extendedLagrangian = True, reflectingBoundary = False,
+            unit = 'namd'
+        ):
+        """r distance template
+
+        Args:
+            setBoundary (bool): whether set boundary (for free-energy calculation)
+            lowerBoundary (float): lower boundary of free-energy calculaton
+            upperboundary (float): upper boundary of free-energy
+            extendedLagrangian (bool, optional): Whether extended Lagrangian is added. Default to True
+            reflectingBoundary (bool, optional): Whether use reflecting boundaries, requires setBoundary on. Default to False
+            unit (str, optional): unit, 'namd' or 'gromacs'. Default to namd.
+        
+        Returns:
+            str: string of distance r definition
+        """
+        
+        if unit == 'namd':
+            scaleFactor = 1
+        elif unit == 'gromacs':
+            scaleFactor = 0.1
+        
+        string = f'\
+colvar {{                            \n\
+    name    r                        \n'
+        if setBoundary:
+            string += f'\
+    width {0.1 * scaleFactor:.2f}                        \n\
+    lowerboundary {lowerBoundary * scaleFactor:.2f}    \n\
+    upperboundary {upperBoundary * scaleFactor:.2f}    \n'
+    
+        if setBoundary and reflectingBoundary:
+            string += f'\
+    reflectingLowerboundary  on              \n\
+    reflectingUpperboundary  on              \n'
+        
+        if extendedLagrangian:
+            string += f'\
+    subtractAppliedForce on          \n\
+    expandboundaries  on             \n\
+    extendedLagrangian on            \n\
+    extendedFluctuation {0.1 * scaleFactor:.2f}          \n'
+
+        string += f'\
+    distance {{                            \n\
+        forceNoPBC       yes               \n\
+        group1 {{                          \n\
+            indexGroup  reference          \n\
+	    }}                                 \n\
+        group2 {{                          \n\
+            indexGroup  ligand             \n\
+        }}                                 \n\
+    }}                                     \n\
+}}                                         \n'
+
+        return string
+
+    def cvHeadTemplate(self, indexFile, reweightAMD=False):
+        """return the head of colvars file
+
+        Args:
+            indexFile (str): name of ndx file
+            reweightAMD (bool, optional): if reweightAMD, there should be "smp off" in the 
+                                          head. Default to False.
+
+        Returns:
+            str: head of colvars file
+        """
+        
+        string = f'\
+colvarsTrajFrequency      5000             \n\
+colvarsRestartFrequency   5000            \n\
+indexFile                 {indexFile}      \n'
+#        if reweightAMD:
+#            string += f'\
+#smp                       off              \n'
+        return string
+
+    def cvHarmonicWallsTemplate(self, cv, lowerWall, upperWall, unit = 'namd'):
+        ''' template of harmonic wall bias
+        
+        Args:
+            cv (str): name of the colvars
+            lowerWall (float): lower wall of the bias
+            upperWall (float): upper wall of the bias
+            unit (str, optional): unit, 'namd' or 'gromacs'. Default to namd.
+                
+        Returns:
+            str: string of the harmonic wall bias definition '''
+        
+        if cv == 'RMSD' or cv == 'r':
+            distanceCV = True
+        else:
+            distanceCV = False
+            
+        if unit == 'gromacs' and distanceCV:
+            scaleFactor = 0.1
+        else:
+            scaleFactor = 1
+            
+        string = f'\
+harmonicWalls {{                           \n\
+    colvars           {cv}                 \n\
+    lowerWalls        {lowerWall * scaleFactor:.1f}      \n\
+    upperWalls        {upperWall * scaleFactor:.1f}      \n\
+    lowerWallConstant 0.2                  \n\
+    upperWallConstant 0.2                  \n\
+}}                                         \n'
+        return string
+
+    def cvHarmonicTemplate(
+            self, cv, constant, center, tiWindows=0, tiForward=True, targetForceConstant = 0,
+            unit = 'namd'
+        ):
+        """template for a harmonic restraint
+
+        Args:
+            cv (str): name of the colvars
+            constant (float): force constant of the restraint
+            center (float): center of the restraint
+            tiWindows (int): number of windows of the TI simulation (if runs a TI simulation). Defaults to 0.
+            tiForward (bool, optional): whether the TI simulation is forward (if runs a TI simulation). Defaults to True.
+            targetForceConstant (int, optional): targeted force constant of the restraint in TI simulation (if runs a TI simulation).
+                                                 Defaults to 0.
+            unit (str, optional): unit, 'namd' or 'gromacs'. Default to namd.
+        
+        Returns:
+            str: string of the harmonic restraint definition
+        """
+        
+        if cv == 'RMSD' or cv == 'r':
+            distanceCV = True
+        else:
+            distanceCV = False
+        
+        if unit == 'gromacs' and distanceCV:
+            forceConstantScaleFactor = 418.4
+            centerScaleFactor = 0.1
+        elif unit == 'gromacs' and not distanceCV:
+            forceConstantScaleFactor = 4.164
+            centerScaleFactor = 1
+        else:
+            forceConstantScaleFactor = 1
+            centerScaleFactor = 1
+            
+
+        string = f'\
+harmonic {{                          \n\
+    colvars         {cv}             \n\
+    forceConstant   {constant * forceConstantScaleFactor:.1f}   \n\
+    centers         {center * centerScaleFactor:.1f}     \n'
+        
+        if tiWindows != 0:
+            string += f'\
+    targetNumSteps      500000                       \n\
+    targetEquilSteps    100000                       \n\
+    targetForceConstant {targetForceConstant * forceConstantScaleFactor:.1f}        \n\
+    targetForceExponent 4                            \n'
+
+            schedule = ''
+            if tiForward:
+                schedule += ' '.join([str(float(i) / float(tiWindows)) for i in range(tiWindows+1)])
+            else:
+                schedule += ' '.join([str(float(i) / float(tiWindows)) for i in range(tiWindows, -1, -1)])
+            
+            string += f'    lambdaSchedule {schedule}\n'
+
+        string += '}\n'
+        return string
+
+    def cvABFTemplate(self, cv, unit='namd', czar=True):
+        ''' template for WTM-eABF bias
+        
+        Args:
+            cv (str): name of the colvars
+            unit (str, optional): unit, 'namd' or 'gromacs'. Default to namd.
+            czar (bool, optional): whether call the czar estimator. Default to True.
+            
+        Returns:
+            str: string of the WTM-eABF definition '''
+            
+        if unit == 'namd':
+            scaleFactor = 1
+        elif unit == 'gromacs':
+            scaleFactor = 4.184
+
+        czar_line = '    writeCZARwindowFile           \n' if czar else ''
+            
+        string = f'\
+abf {{                            \n\
+    colvars        {cv}           \n\
+    FullSamples    10000          \n\
+    historyfreq    50000          \n\
+{czar_line}\
+}}                                \n\
+metadynamics {{                   \n\
+    colvars           {cv}        \n\
+    hillWidth         3.0         \n\
+    hillWeight        {0.05 * scaleFactor:.2f}        \n\
+    wellTempered      on          \n\
+    biasTemperature   4000        \n\
+}}                                \n'
+        return string
+    
+    def cvHistogramTemplate(self, cv):
+        """ template for outputting the histogram of the CV
+
+        Args:
+            cv (str): name of the colvars
+            
+        Returns:
+            str: string of the histogram definition
+        """
+        
+        string = f'\
+histogram {{                     \n\
+  colvars    {cv}                \n\
+  outputFileDX  none             \n\
+  outputFreq 10000               \n\
+}}                               \n'
+        return string
+
+    def cvReweightAMDTemplate(self, cv):
+        """ template for reweight aMD results
+
+        Args:
+            cv (str): name of the colvars
+            
+        Returns:
+            str: string of the reweightamd definition
+        """
+        
+        string = f'\
+reweightamd {{                  \n\
+  colvars  {cv}                 \n\
+}}                              \n'
+        return string
+
+    def cvProteinTemplate(self, centerCoor, refFile, unit = 'namd'):
+        """the template of restraining the protein
+
+        Args:
+            centerCoor (np.array, 3): (x,y,z), center of the protein 
+            refFile (str): path of the reference file
+            unit (str, optional): unit, 'namd' or 'gromacs'. Default to namd.
+        
+        Returns:
+            str: string of the restraining the protein
+        """
+        
+        if unit == 'namd':
+            translationCoorScaleFactor = 1
+            translationForceScaleFactor = 1
+            orientationForceScaleFactor = 1
+        elif unit == 'gromacs':
+            translationCoorScaleFactor = 0.1
+            translationForceScaleFactor = 418.4
+            orientationForceScaleFactor = 4.184
+        
+        string = f'\
+colvar {{                         \n\
+  name translation                \n\
+  distance {{                     \n\
+    group1 {{                     \n\
+      indexGroup  protein         \n\
+    }}                            \n\
+    group2 {{                     \n\
+      dummyAtom ({centerCoor[0] * translationCoorScaleFactor}, {centerCoor[1] * translationCoorScaleFactor}, {centerCoor[2] * translationCoorScaleFactor})    \n\
+    }}                            \n\
+  }}                              \n\
+}}                                \n\
+harmonic {{                       \n\
+  colvars       translation       \n\
+  centers       0.0               \n\
+  forceConstant {100.0 * translationForceScaleFactor:.1f}             \n\
+}}                                \n\
+                                  \n\
+colvar {{                         \n\
+  name orientation                \n\
+  orientation {{                  \n\
+    atoms {{                      \n\
+      indexGroup  protein         \n\
+    }}                            \n\
+    refPositionsFile   {refFile}  \n\
+  }}                              \n\
+}}                                \n\
+harmonic {{                       \n\
+  colvars       orientation       \n\
+  centers       (1.0, 0.0, 0.0, 0.0)    \n\
+  forceConstant {2000.0 * orientationForceScaleFactor:.1f}            \n\
+}}                                \n'
+        return string