@WAMM
################################################################################
# Location and features of input and output directories / file(s)
#
# Location and features of input and output directories / file(s)
#
# lig_struct_path: Folder containing the ligand input file(s)
# multi_structure_lig_file: Basename of ligand file, if multi-structure
#                           file is provided
# output_path: Basis directory in which all setup and analysis
#              folders will be generated
# rec_structure: Receptor structure in PDB format
# bound_rec_structure: Optional, alternative receptor structure in bound
#                      conformation to be used for 3-trajectory approach
lig_struct_path              /home/user/tutorial/structs
multi_structure_lig_file
output_path                  /home/user/tutorial
rec_structure                /home/user/tutorial/input_info/2RA0_IN.pdb
bound_rec_structure

# Specification of ligand input format
lig_format_sdf               0
lig_format_mol2              1

# Receptor features
# water_in_rec: Water present in receptor PDB structure
water_in_rec                 1

# Request structure separation
# structure_separation: Separate ligands specified in one multi-structure #                       input file and generate one structure file per ligand.
structure_separation         0

################################################################################
# Creation of LEaP input files
#
# prepare_leap_input: Generate files for LEaP input
# non_neutral_ligands: Total charge of at least one molecule is not zero.
#                      In this case the total charge of each non-neutral
#                      molecule must be defined in lig_charge_file.
# lig_charge_file: File with information about total charges of ligands.
# am1_lig_charges: Calculate AM1-BCC charges.
# resp_lig_charges: Calculate RESP charges. In this case charges must be
#                   computed with the program Gaussian in an intermediate step.
#                   Batch scripts for Gaussian calculations will be prepared
#                   automatically, if requested (see prepare_gauss_batch_file
#                   and gauss_batch_template below).
# calc_charges: Calculate charges according to requested procedure.
#               If this flag is set to zero, no atomic charges are calculated.
# resp_setup_step1: Step 1 of RESP charge calculation: Preparation of
#                   Gaussian input.
# resp_setup_step2: Step 2 of RESP charge calculation: Generation of LEaP input #                   from Gaussian output.
# prepare_gauss_batch_file: Generate batch script for Gaussian input if RESP
#                           charge calculation is performed. A batch template
#                           file (gauss_batch_template) is required.
# gauss_batch_template: Batch template file
#                       Prerequisite: resp_lig_charges=1, resp_setup_step1=1
#                       and prepare_gauss_batch_file=1
# gauss_batch_path: Basic working directory for Gaussian jobs
# average_charges: If the charges of two steroisomers shall be averaged, so that
#                  both ligands obtain the same atomic charges, a file in which
#                  the stereoisomer pairs are specified must be given here.
prepare_leap_input           1
non_neutral_ligands          0
lig_charge_file
am1_lig_charges              1
resp_lig_charges             0
calc_charges                 1
resp_setup_step1             0
resp_setup_step2             0
prepare_gauss_batch_file     0
gauss_batch_template
gauss_batch_path
average_charges

@WAMM
################################################################################
# Location and features of input and output directories / file(s)
#
# lig_struct_path: Folder containing the ligand input file(s)
# multi_structure_lig_file: Basename of ligand file, if multi-structure
#                           file is provided
# output_path: Basis directory in which all setup and analysis
#              folders will be generated
# rec_structure: Receptor structure in PDB format
# bound_rec_structure: Optional, alternative receptor structure in bound
#                      conformation to be used for 3-trajectory approach
lig_struct_path               /home/user/tutorial/structs
multi_structure_lig_file
output_path                   /home/user/tutorial
rec_structure                 /home/user/tutorial/input_info/2RA0_IN.pdb
bound_rec_structure

# Specification of ligand input format
lig_format_sdf 0
lig_format_mol2 1

# Receptor features
# water_in_rec: Water present in receptor PDB structure
water_in_rec 1

################################################################################
# Setup of molecular dynamics simulations
#
# setup_MDsimulations: Perform setup of simulation input
# traj_setup_method: 1 = One trajectory approach
#                    3 = Three trajectory approach
# MD_am1: Prepare simulations with AM1-BCC charges
# MD_resp: Prepare simulations with RESP charges
# SSbond_file: File with disulfide bridge definitions
# additional_library: If an additional library file is required, e.g. for
#                     non-standard residues present in the receptor structure,
#                     this file must be specified here.
# additional_frcmod: If additional parameters are needed, e.g. for describing
#                    non-standard residues present in the receptor structure,
#                    a parameter file should be provided here.
# MD_batch_path: Path to basis directory in which the simulations shall
#                be performed in case this differs from <output_path>.
#                If no path is given, it is assumed that the path is #                equal to <output_path>
# MDequil_template_folder: Path to directory with equilibration template files
# total_MDequil_time: Total equilibration time in ps
# MDequil_batch_template: Batch template file for equilibration
# MDprod_template: Template file for production phase of MD simulation
# total_MDprod_time: Number of ns to simulate
# MDprod_batch_template: Batch template file for MD production
# no_of_rec_residues: Number of residues in receptor structure
# restart_file_for_MDprod: Base name of restart-file from equilibration that
#                          shall be used for production input
setup_MDsimulations         1
traj_setup_method           3
MD_am1                      1
MD_resp                     0
SSbond_file                 /home/user/tutorial/input_info/disulfide_bridges.txt
additional_library          /home/user/tutorial/input_info/CA.lib
additional_frcmod
MD_batch_path
MDequil_template_folder     /home/user/tutorial/input_info/equi
total_MDequil_time          400
MDequil_batch_template      /home/user/tutorial/input_info/equi.pbs
MDprod_template             /home/user/tutorial/input_info/MD_prod.in
total_MDprod_time           2
MDprod_batch_template       /home/user/tutorial/input_info/prod.pbs
no_of_rec_residues          290
restart_file_for_MDprod     md_nvt_red_06

@WAMM
################################################################################
# Command file for MM-PBSA / MM-GBSA calculations based on trajectories
# generated by molecular dynamics simulations previously.
################################################################################
# Location and features of input and output directories / file(s)
#
# lig_struct_path: Folder containing the ligand input file(s)
# output_path: Basis directory in which all setup and analysis folders will
#              be generated. The directory needs to be identical with the
#              'output_path' directory used for setup of the MD simulations.
lig_struct_path               /home/user/tutorial/structs
output_path                   /home/user/tutorial

# Receptor features
# water_in_rec: Water present in receptor PDB structure
# used for setup of MD simulations
water_in_rec                  1

################################################################################
# General Parameters for MM-PBSA / MM-GBSA calculation setup
#
# mmpbsa_calc: Setup MM-PBSA / MM-GBSA calculations
# 1_or_3_traj: "1" or "3" trajectory approach
# charge_method: Charge method used for MD, either "resp" or "am1"
# additional_library: If an additional library file is required, e.g. for
#                     non-standard residues present in the receptor structure,
#                     this file must be specified here.
# additional_frcmod: If additional parameters are needed, e.g. for describing
#                    non-standard residues present in the receptor structure,
#                    a parameter file should be provided here.
# mmpbsa_pl: Path to mm_pbsa.pl script
mmpbsa_calc             1
1_or_3_traj             3
charge_method           am1
additional_library      /home/user/tutorial/input_info/CA.lib
add_frcmod
mmpbsa_pl               $AMBERHOME/bin/mm_pbsa.pl
################################################################################
# Parameters for coordinate (snapshot) extraction
#
# extract_snapshots: Request coordinate (snapshot) extraction
# snap_extract_template: Template file for extraction of coordinates from
#                        trajectory, i.e. input-file for mm_pbsa.pl; only
#                         required if non-standard input-file shall be used.
# image_trajectories: If set to "1" solutes of the specified trajectories
#                      will be imaged to the origin before coordinates are
#                      extracted. Please regard that this may require a large
#                      amount of additional disc space.
# trajectory_files: Trajectory files to regard. The path will be determined
#                   automatically. Specify 'all' to regard all trajectories
#                   files produced in MD. This ensures consistent snapshot
#                   numbering. Subsets of snapshots will be generated according
#                   to the parameters first_snapshot, last_snapshot, and
#                   offset_snapshots. If only a subset of the available MD
#                   trajectories shall be used, the individual files must be
#                   specified as 'trajectory_files ' providing
#                   one entry per line.
# first_snapshot: First structure that shall be extracted from trajectory
# last_snapshot: Last structure that shall be extracted from trajectory
# offset_snapshots: Frequency of structure extraction
#
snap_extract_template
image_trajectories          1
#
trajectory_files            all
#
first_snapshot              1
last_snapshot               100
offset_snapshots            1
################################################################################
# MM-PBSA / MM-GBSA Analysis
# mmpbsa_template: Template file for MM-PBSA / MM-GBSA analysis - File used
#                  as input-file for mm_pbsa.pl; only required if non-standard
#                  file shall be used.
# PB: If not zero PB calculation will be performed
#     Options: "0" -> No PB
#              "1" -> PB with calculation of the non-polar part of the
#                     solvation free energy using the Method developed by
#                     Tan et al. (J. Phys. Chem. B, 2007, 111, 12263-12274).
#                     This method can only be run in combination with GB=1
#                     or GB=0.
#              "2" -> Hybrid model developed by H. Gohlke and A. Metz
#                     with IVCAP=5 and CUTCAP=50
#              "3" -> PB with MS=1 and Parse radii
#              "4" -> PB with MS=1 and mbondi radii. This method can only
#                     be combined with GB=1 or GB=0.
# GB: If not zero GB calculation will be performed
#     Options: "0" -> No GB
#              "1", "2", "5" -> GB analysis according to 'igb' (see manual)
#
# decomposition: If larger 0 energy decomposition of specified type is
#                performed. Options: 1-4 - See Amber manual for decomposition
#                type options. Decomposition only works with PB=4 and GB=1.
#                SASA is calculated by the ICOSA method.
# no_of_rec_residues: Number of residues in the receptor structure
#
# total_no_of_intervals: Total number of intervals to analyze.
#                        The total_no_of_intervals needs to be consistent with
#                        the number of 'first_PB_snapshot', 'last_PB_snapshot',
#                        and 'offset_PB_snapshots' definitions below. Setting
#                        total_no_of_intervals to a value larger than 1, is
#                        usually only necessary if snapshots with different
#                        offsets shall be analyzed.
# first_PB_snapshot: Structure to start analysis with
# last_PB_snapshot: Last structure to regard in analysis
# offset_PB_snapshots: Specification of offset between structures that shall
#                      be regarded in the MM-PBSA calculation
#
# mmpbsa_batch_template: Batch script template for MM-PBSA calculation
# mmpbsa_batch_path: Optional, path to regard as basis path for batch script
#                    setup, in case it differs from .
#
# mmpbsa_sander_exe: Optional, Sander executable can be defined here if not
#                    the default executable in $AMBERHOME/bin shall be
#                    used for carrying out the MM-PB(GB)SA calculations.
# parallel_mmpbsa_calc: No. of processors to use for parallel run
mmpbsa_template
PB                        0
GB                        2
#
decomposition             0
no_of_rec_residues        290
#
total_no_of_intervals     1
first_PB_snapshot         51
last_PB_snapshot          100
offset_PB_snapshots       1
#
mmpbsa_batch_template     /home/user/tutorial/input_info/MMPBSA.sge
mmpbsa_batch_path         /home/user/tutorial
#
mmpbsa_sander_exe
parallel_mmpbsa_calc      1

@LIEW
################################################################################
# Command file for LIE calculations based on trajectories
# generated by molecular dynamics simulations previously.
################################################################################
# Location and features of input and output directories / file(s)
#
# lig_struct_path: Folder containing the ligand input file(s)
# output_path: Basis directory in which all setup and analysis folders will
#              be generated. The directory needs to be identical with the
#              'output_path' directory used for setup of the MD simulations.
lig_struct_path              /home/user/tutorial/structs output_path                  /home/user/tutorial

# Receptor features
# water_in_rec: Water present in receptor PDB structure
#               used for setup of MD simulations
water_in_rec                 1

################################################################################
# General Parameters for LIE calculation setup
#
# lie_calc: Request setup of LIE calculations
# charge_method: Charge method used for MD, either "resp" or "am1"
# no_of_rec_residues: Number of residues in receptor structure
# additional_library: If an additional library file is required, e.g. for
#                     non-standard residues present in the receptor structure,
#                     this file must be specified here.
# additional_frcmod: If additional parameters are needed, e.g. for describing
#                    non-standard residues present in the receptor structure,
#                    a parameter file should be provided here.
# lie_executable: Location of LIE calculation script provided with FEW.
#                 If no script is specified, it is assumed that the LIE
#                 program is located in the default directory.
# lie_batch_template: Template batch file for LIE calculation
# lie_batch_path: Path to regard as basis path for setup of batch files
#
lie_calc                1
charge_method           am1
no_of_rec_residues      290
additional_library      /home/user/tutorial/input_info/CA.lib
additional_frcmod
lie_executable
lie_batch_template      /home/user/tutorial/input_info/lie.sge
lie_batch_path
#
################################################################################
# Parameters for coordinate extraction
#
# image_trajectories: If set to "1" solutes of the specified trajectories
#                     will be imaged to the origin before coordinates are
#                     extracted. Please regard that this may require a large
#                     amount of additional disc space.
# trajectory_files: Trajectory files to regard. The path will be determined
#                   automatically. Specify 'all' to regard all trajectories
#                   produced in the production phase of the MD simulations.
#                   This ensures consistent snapshot numbering.
#                   Subsets of snapshots will be generated according to the
#                   parameters first_lie_snapshot, last_lie_snapshot, and
#                   offset_lie_snapshots. If only a subset of the trajectories
#                   from MD shall be used, the individual files must be
#                   specified as 'trajectory_file ' providing one
#                   entry per line.
#                   ATTENTION: The trajectory file(s) must exist for both the
#                              simulation of the complex and the simulation of
#                              the free ligand in solution.
# snaps_per_trajectory: Number of snapshots stored in each trajectory.
#
image_trajectories        1
#
trajectory_files          md_prod_001.mdcrd.gz
trajectory_files          md_prod_002.mdcrd.gz
#
snaps_per_trajectory      50
################################################################################
# LIE Analysis
#
# calc_sasa: Request calculation of change in solvent accessible surface area
# first_lie_snapshot: No. of snapshot from which the LIE calculation
#                     shall be started
# last_lie_snapshot: No. of last snapshot that shall be regarded in the
#                    LIE calculation
# offset_lie_snapshots: Offset between snapshots that shall be regarded
#                       in the LIE calculation
# sander_executable: Sander executable that shall be used for the LIE
#                    calculation, if this differs from the default one
#                    in $AMBERHOME/bin
# parallel_lie_call: Call for running sander in parallel, e.g.:
#                    mpirun -np 2 -machinefile $PBS_NODEFILE
#                    Prerequisite: Parallel version of sander installed
# delete_lie_trajectories: Delete trajectory files created for LIE analysis
#                          directly after energy calculation
#
calc_sasa                    0
first_lie_snapshot           81
last_lie_snapshot            100
offset_lie_snapshots         1
sander_executable
parallel_lie_call            mpirun -np 8
delete_lie_trajectories      0

@TIW
################################################################################
# Command file for TI simulation setup
################################################################################
# Location of input and output directories / file(s)
#
# lig_struct_path: Folder containing the ligand input file(s)
# output_path: Basis directory in which all setup and analysis folders will
#              be generated. The directory must be identical with the
#              'output_path' directory used for setup of the MD simulations.
lig_struct_path              /home/user/tutorial/structs
output_path                  /home/user/tutorial

################################################################################          
# Parameters required for TI simulation setup: 
# The following parameters have to be specified and need to be identical
# in all subsequent runs for one system / TI-setup
#
# ti_simulation_setup: Request setup of TI simulation
# charge_method: Charge method that shall be used, either "resp" or "am1"
# lig_name_v0_struct: Name of start-ligand - Must be identical to the name of
#                     the file in the "structs" folder used for generation of
#                     parameter and library files with the common MD setup
#                     functionality of FEW.
# lig_name_v1_struct: Name of end-ligand - Must be identical to the name of
#                     the file in the "structs" folder used for generation of
#                     parameter and library files with the common MD setup
#                     functionality of FEW.
# lig_alias_v0: Alias that shall be used for the identification of the
#               start-ligand. The alias must consist of 3 characters.
# lig_alias_v1: Alias that shall be used for the identification of the
#               end-ligand. The alias must consist of 3 characters.
# softcore_mask_v0: Soft core atom mask for start-structure, specifying the
#                   atoms of the start-structure (state V0) that shall be
#                   regarded as soft core using the format
#                   <lig_alias_v0>@<atom name list separated by comma>
# softcore_mask_v1: Soft core atom mask for end-structure, specifying the
#                   atoms of the end-structure (state V1) that shall be
#                   regarded as soft core using the format
#                   <lig_alias_v1>@<atom name list separated by comma>
ti_simulation_setup         1
charge_method               am1
lig_name_v0_struct          L51c
lig_name_v1_struct          L51d
lig_alias_v0                LFc
lig_alias_v1                LFd
softcore_mask_v0            LFc@C14,H1
softcore_mask_v1            LFd@N3
#
################################################################################
# 1) Parameters for preparation of coordinate and topology files of solvated
#    systems of start- and end-structures for TI simulations
#
# A) Generation of atom association list based on ligand mol2 files of
#    start and end structures
#
# prepare_match_list: Request creation of matching list
prepare_match_list          1
#
# B) Setup of coordinate and topology files
#
# It is required that RESTRT (coordinate) and topology files for the ligand and
# complex of the start structure exist. These can be generated with the common
# MD setup functionality of FEW.
#
# prepare_inpcrd_prmtop: Request setup of coordinate and topology files
# lig_inpcrd_v0: Coordinate file (restart file) of ligand - start structure
# com_inpcrd_v0: Coordinate file (restart file) of complex - start structure
# lig_prmtop_v0: Topology of ligand - start structure
# com_prmtop_v0: Topology of complex - start structure
# match_list_file: Optional: File containing the atom association information
#                  for the common part of start- and end-structures. Must only
#                  be specified if step 1A was not successful and the list was
#                  created manually.
# chain_termini: Comma separated numbers of terminal residues of chains in
#                receptor structure.
# create_sybyl_mol2: Request generation of mol2-files with sybyl atom types
#                    for easy comparison of atom names of start- and end-
#                    structures. Can facilitate checking and manual adjustment
#                    of atom names in the end-structure, if automatic matching
#                    is not successful.
# additional_library: If an additional library file is required, e.g. for
#                     non-standard residues present in the receptor structure,
#                     this file must be specified here.
# additional_frcmod: If additional parameters are needed, e.g. for describing
#                    non-standard residues present in the receptor structure,
#                    a parameter file should be provided here.
# SSbond_file: File with disulfide bridge definitions
#              
prepare_inpcrd_prmtop      1
lig_inpcrd_v0              /home/user/tutorial/MD_am1/L51c/lig/equi/md_nvt_red_06.restrt
com_inpcrd_v0              /home/user/tutorial/MD_am1/L51c/com/equi/md_nvt_red_06.restrt
lig_prmtop_v0              /home/user/tutorial/MD_am1/L51c/cryst/L51c_solv_lig.top
com_prmtop_v0              /home/user/tutorial/MD_am1/L51c/cryst/L51c_solv_com.top
match_list_file
chain_termini              235
create_sybyl_mol2          1
additional_library         /home/user/tutorial/input_info/CA.lib
additional_frcmod
SSbond_file                /home/user/tutorial/input_info/disulfide_bridges.txt

# 2) Setup scripts for TI MD
#
# General parameters
#
# no_shake: Set to "1", if no SHAKE shall be performed
# ti_batch_path: Root path to be used in setup of batch files
# ti_prod_template: Template script for TI production simulations
no_shake                   1
ti_batch_path              /home/user/tutorial
ti_prod_template           /home/user/tutorial/input_info/MD_prod_noShake_TI.in
#
# A) Setup of scripts for equilibration
#
# ti_equil: Request generation of scripts for TI equilibration input
# ti_equil_template: Template file for equilibration part of equilibration
#                    phase of TI simulations. This equilibration part is
#                    followed per default by a 1 ns free TI MD simulation
#                    for complete equilibration of the system.
# ti_equil_batch_template: Batch template file for equilibration phase of
#                          TI simulations.
# ti_equil_lambda: Values of lambda that shall be used in the calculation
#                  in ascending order. Please specify only the decimal digits,
#                  e.g. 1 for lambda 0.1, 05 for lambda 0.05.
ti_equil                   0
ti_equil_template          /home/user/tutorial/input_info/equi_noShake_TI.in
ti_equil_batch_template    /home/user/tutorial/input_info/equi_TI.sge
ti_equil_lambda            1,2,3,4,5,6,7,8,9
#
# B) Setup scripts for production
#
#    ATTENTION: This setup step can only be conducted if the equilibration
#               calculations have been completed.
#
# ti_production: Request generation of scripts for TI production input.
#                This setup step requires that the equilibration output is
#                present in the corresponding 'equi' folder.
# ti_prod_lambda: Lambda steps for which the production shall be run;
#                 separated by comma and in ascending order. Please specify
#                 only the decimal digits, e.g. 1 for lambda 0.1.
# total_ti_prod_time: Total production time requested (in ns)
# ti_prod_batch_template: Batch template for TI production simulations
# converge_check_script: Location of perl program to be used for convergence
#                        checking after each production step. If the location
#                        is not specified, it will be assumed that the program
#                        can be found under the default location
#                        at .../FEW/miscellaneous/convergenceCheck.pl
# converge_check_method: Method that shall be used for convergence checking.
#                        1: Difference in standard error of dV/dL
#                        2: Precision of dV/dL according to student's
#                           distribution
# converge_error_limit: Error limit that shall be used as termination criterion
#                       for the TI production simulations.
#                       Defaults: 0.01 kcal/mol for method 1
#                                 0.2 kcal/mol for method 2
ti_production              0
ti_prod_lambda             1,2,3,4,5,6,7,8,9
total_ti_prod_time         1,1,1,1,1,1,1,1,1
ti_prod_batch_template     /home/user/tutorial/input_info/prod_TI.sge
converge_check_script
converge_check_method      2
converge_error_limit       0.2

@TIW
################################################################################
# Command file for calculating the difference in binding free energy
# between start and end ligand based on TI simulations.
################################################################################
# Location of input and output directories / file(s)
#
# lig_struct_path: Folder containing the ligand input file(s)
# output_path: Basis directory in which all setup and analysis folders will
#              be generated. The directory must be identical with the
#              'output_path' directory used for setup of the MD simulations.
lig_struct_path              /home/user/tutorial/structs
output_path                  /home/user/tutorial

################################################################################
# Parameters required for TI analysis:
#
# ti_ddG: Request calculation of difference in binding free energy.
# charge_method: Charge method that shall be used, either "resp" or "am1"
# lig_name_v0_struct: Name of start-ligand - Must be identical to the name of
#                     the file in the "structs" folder used for generation of
#                     parameter and library files with the common MD setup
#                     functionality of FEW.
# lig_name_v1_struct: Name of end-ligand - Must be identical to the name of
#                     the file in the "structs" folder used for generation of
#                     parameter and library files with the common MD setup
#                     functionality of FEW.
# lig_alias_v0: Alias that shall be used for the identification of the
#               start-ligand. The alias must consist of 3 characters.
# lig_alias_v1: Alias that shall be used for the identification of the
#               end-ligand. The alias must consist of 3 characters.
# dVdL_calc_source: Specification of files considered in computation of ddG:
#                   0: All files available for ligand and complex are considered
#                   X-Y: Where X is the number of the first and Y is the number
#                   of the last production file that shall be taken into account.
#                   If Y=0 all files from X on will be considered.
# ddG_calc_method: Method to be used for the calculation of dG:
#                  1: Conventional numerical integration with interpolation
#                     to lambda=0 and lambda=1.
#                  2: Numerical integration without interpolation
#
ti_ddG                      1
charge_method               am1
lig_name_v0_struct          L51c
lig_name_v1_struct          L51d
lig_alias_v0                LFc
lig_alias_v1                LFd
dVdL_calc_source            0
ddG_calc_method             1