Description

PepBD_Plastics is a Fortran program that discovers polypeptides predicted to have affinity for common plastics using Monte Carlo sampling and atomistic biophysical modeling.

Required input files

All should be placed in the directory for running PepBD, unless otherwise noted. Examples are provided in the repository

• compiled executable
• input.txt (see below for details)
• sys.pdb (see below for details)
• the lib folder, placed at the location ~/PepBD/
• A directory named pdbfiles

Installation and Compilation

Requirements: Intel ifort compiler (tested on versions 2017 - 2024)

1. Navigate to the directory with PepBD_Plastics.f90
2. Determine the total number of residues, num_residues in sys.pdb
3. Replace gnum=0 in with gnum=num_residues in PepBD_Plastics.f90 file.
4. Run the command ifort -O2 -o main PepBD_Plastics.f90

Running PepBD_Plastics

Run from a terminal using ./main. Note that PepBD_Plastics is a serial program.

The runtime depends on the system size and number of design steps, but normally takes a day to a week to complete.

Output of PepBD_Plastics

Examples of each output are provided in the repository

1. energyprofile.txt: score and energy components at each PepBD step
2. energydetails.txt: sequence, energy, and move type at each PepBD step
3. output.txt: Details of the PepBD run
4. Generated pdbs: stored in the pdbfiles directory
5. rmsd.txt: the rmsd relative to the starting state at each step of design. This is disabled in PepBD_Plastics.f90, so 0 is output at every step.

Details on required files

input.txt

The file must be named input.txt. The following variables that can be specified

• PDBFILE (required): the name of the pdb file containing the peptide-receptor complex
• RESTARTPDB (required): the name of the pdb file if restarting PEPBD halfway through design. If starting at beginning of design, then name should match PDBFILE
• RECALCUSWITCH (required): Specifies if design is starting at beginning or being restarted from previous run. Set to 0 if starting from beginning, 1 otherwise. If set to 1, then the coordinates in "RESTARTPDB" will be used as the starting point for design
• STEP_START (required): Beginning step number of PepBD design. Set to 0 if starting design from beginning. Not used if SA_FLAG is set to 1, but still required.
• STEP_END (required): Final step number of PepBD design. Not used if SA_FLAG is set to 1, but still required.
• SITENUM (required): Number of residues in the peptide.
• RECEPTOR_NAME (required): Type of receptor. Options are nucleic, peptide, or other
• BACKBONE_CHANGE_PROB (required): Probability of making a change to peptide backbone for a given PepBD step.
• SEQ_CHANGE_PROB (required): Probability of making a change to the peptide sequence for a given PepBD step.
• SCMF_SWITCH (default=0.8): For a peptide sequence change, the probability that the change is changing an amino acid rather than switching two amino acids
• KT_SEQUENCE (required): The reference temperature for peptide sequence changes used in the Metropolis acceptance criterion.
• KT_BACKBONE_RATIO (required): Ratio of reference temperature for backbone changes to reference temperature fo sequence changes
• pH (required): pH of system. Hydration state of peptide and receptor should match the system pH
• RANSEED (required): seed to random number generator
• MIN_RMSD (required): Minimum RMSD limit for peptide backbone
• MAX_RMSD (required): Maximum RMSD limit for peptide backbone
• NUM_GLY_MIN (required): Lower limit on number of glycine that must be in peptide sequence
• NUM_GLY_MAX (required): Upper limit on number of glycine that must be in peptide sequence
• NUM_PHOBIC_MIN (required): Lower limit on number of hydrophobic residues that must be in peptide sequence
• NUM_PHOBIC_MAX (required): Upper limit on number of hydrophobic residues that must be in peptide sequence
• NUM_PHIL_MIN (required): Lower limit on number of hydrophilic residues that must be in peptide sequence
• NUM_PHIL_MAX (required): Upper limit on number of hydrophilic residues that must be in peptide sequence
• NUM_NEG_MIN (required): Lower limit on number of anionic residues that must be in peptide sequence
• NUM_NEG_MAX (required): Upper limit on number of anionic residues that must be in peptide sequence
• NUM_POS_MIN (required): Lower limit on number of cationic residues that must be in peptide sequence
• NUM_POS_MAX (required): Upper limit on number of cationic residues that must be in peptide sequence
• NUM_OTHER_MIN (required): Lower limit on number of other residues that must be in peptide sequence
• NUM_OTHER_MAX (required): Upper limit on number of other residues that must be in peptide sequence
• TRP_LIMIT (default=3): Upper limit on number of tryptophan in the peptide sequence
• NUM_HELIX (required): Number of helices in the peptide
• STEP_BEFORE_CONF_CHANGE (default=50): Number of PepBD steps to take before changes to the peptide backbone are allowed
• PDB_GEN_FREQ (default=50): Number of PepBD steps taken before a pdb file of system is changed. Note that pdb files are also saved whenever the PepBD score is the lowest out of all sequences/backbones sampled
• PEP_WEIGHT_FACTOR (default=0.01): Factor that multiplies peptide-peptide interactions when calculating the PepBD score
• INITIAL_RANDOMIZE (default=0): If 1, then peptide sequence is randomized before starting PepBD design. If 0, then the sequence is not randomized
• SA_FLAG (default=0): If 1, then use simulated annealing to perform PepBD design. If 0, then use constant temperature.
• SA_INTERVAL (default=100): Number of PepBD steps to perform before reducing reference temperature for sequence and backbone changes
• SA_FRACTION (default=0.9): Factor by which reference temperature is multipled after each SA_INTERVAL
• SA_T_START (default=10): Starting reference system temperature for both sequence and backbone changes. Units of kcal/mol
• SA_T_END (default=0.5): Final reference system temperature for both sequence and backbone changes. Units of kcal/mol

sys.pdb

Contains the peptide-receptor complex. Since PepBD_Plastics takes longer as the system size increases, typically receptor atoms that are 10 Angstroms from the peptide are removed, e.g. using VMD. sys.pdb should be formatted such that

• Only lines for atomic coordinates remain
• The peptide appears first, followed by the receptor