/
primarydock.config
executable file
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/
primarydock.config
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# Sample PrimaryDock configuration file.
#
# Modify this or create fresh.
# Note that every parameter listed in this file can also be given as a command line
# argument, e.g.:
#
# bin/primarydock --lig sdf/helional.sdf --diff test/1a1_citral.config --out output/OR1A1_helional.test.dock # Dock helional using the same settings as for citral.
#
# Note that if you override the PROT parameter, it is also recommended you override
# CEN, PATH, STATE, and EXCL (as applicable) since these will vary slightly from
# protein to protein.
#
# Path to PDB of protein (required):
PROT pdbs/OR1/OR1A1.upright.pdb
# Optional: Add hydrogens to the protein after loading it.
# Strongly recommended if the PDB does not contain hydrogen atoms.
# HYDRO
# Path to PDB or SDF of ligand (required):
LIG sdf/citral.sdf
# Optional SMILES input string. This will override the ligand SDF file.
# It is not recommended to specify a completely different molecule from the SDF file.
# This feature is intended for instances where e.g. a ligand should be docked in an
# ionized state and the SDF contains a neutral uncharged molecule, or an internal
# arrangement of conjugated bonds in the desired ligand differs from the SDF, or any
# other variation not involving the addition or removal of heavy atoms.
# Note that if a --lig argument is specified on the command line, it will override
# any SMILES param in the config file.
# SMILES CC(=CCCC(=CC=O)C)C
# Center of binding pocket (required):
# Can be ABS or RES; default is ABS if unspecified.
# ABS means use literal XYZ coordinates.
# RES means average the CA locations of all indicated
# residue numbers or Ballesteros-Weinstein numbers.
# CEN ABS -4.93883 5.08067 -4.91533
# CEN RES 105 108 202 206 251 258
CEN RES 2.53 3.29 3.32 3.33 3.36 3.37 3.40 3.41 4.53 4.57 4.60 45.49 45.52 5.39 5.43 5.46 5.47 6.48 6.51 7.38 7.39 7.42
# Optional required contact residues. These are residues that the ligand must bind
# to if possible. During dock, the ligand may not pull away from any of these residues
# if the binding energy between the ligand and residue is smaller than 5 kJ/mol.
# These can be thought of more as "sticky" residues rather than mandatory interactions,
# since the behavior is to move closer to each residue until the threshold coordination
# energy is met.
# Each REQSR is tied to a node number, in this case node zero. There is no limit to the
# number of REQSR parameters. If applying a REQSR to all path nodes, it is best to use
# the word ALL in place of a node number, so that the binding energies won't be reset
# between nodes.
# REQSR 0 4.57 4.60 5.39
# Optional path. If given, PrimaryDock will attempt to move the ligand along the
# path and report the binding energy at each node.
# The pocket center is considered to be node zero.
# Nodes must be numbered from 1 to n, where n < 256.
# Path can be ABS, REL, or RES. ABS and RES work the same as CEN above, while
# REL takes relative XYZ coordinates to add to the previous node's coordinates.
# Default is ABS if unspecified - NOTE this is different from the previous behavior
# where REL was the only option, so please update your config files!
# RES is particularly valuable when using STATE params, as detailed below.
# PATH 1 REL -2.0 -2.5 -0.5
# PATH 2 RES 112 206 251
# PATH 3 RES 115 213 244
# PATH 4 RES 59 118 240
# Optional active configuration
# If at least one PATH is specified, and an active node is specified, then during
# docking, when the calculation reaches the indicated path node, the protein will
# be modified by having indicated parts moved and rotated in space. The below lines,
# if uncommented, will affect the region of BW# 6.26 - 6.60, corresponding to
# transmembrane helix 6, as follows: it will be rotated about the 6.48 residue,
# about an axis defined by relative coordinates [-0.55 0 0.84], 20 degrees in the
# positive (clockwise) direction, with no spatial transform (i.e. relative coordinates
# [0 0 0] to be added to all residues in range).
# This corresponds to the active state of an OR per Billesbølle et al (2022).
# https://doi.org/10.1101/2022.12.20.520951
# The active node can have an unlimited number of ACVHXR params.
# ACVNODE 2
# ACVHXR TMR6 6.26 6.60 6.48 0 0 0 -0.55 0 0.84 20
# Optional per-node conformation
# Similar to ACVHXR above, it is possible to define an unlimited number of rotations
# and/or transformations to be applied at specific nodes, without having to limit
# them to a single active state node.
# The below lines, if uncommented, will immediately move TMR6 2A in the +Y direction,
# then rotate it 5 degrees for each subsequent node.
# Note all rotations and transformations are *cumulative*, not absolute; if given two
# consecutive HXR lines each with a 5 degree rotation, the final rotation will be 10
# degrees relative to the original protein structure.
# The format is HXR node region start_resno end_resno pivot_resno transform_xyz axis theta.
# Possible values for the axis include Cartesian (three floating point numbers separated by
# spaces), region region_name, bw bw.number, or atom bw.number:aname.
# HXR 0 TMR6 6.26 6.60 6.48 0 2 0 -0.55 0 0.84 0
# HXR 1 TMR6 6.26 6.60 6.48 0 0 0 region TMR2 5
# HXR 2 TMR6 6.26 6.60 6.48 0 0 0 bw 2.50 5
# HXR 3 TMR6 6.26 6.60 6.48 0 0 0 atom 2.50:CA 5
# Optional protein conformational states.
# If the protein changes shape during path docking, you can indicate which parts of
# the protein move by how much at which path node. An imaginary axis of rotation is
# drawn from the starting residue's CA to the ending residue's CA, then a rotation
# of the indicated number of degrees is performed. The below line, if uncommented,
# would indicate a 25 degree (counterclockwise if viewed from residue 210 looking at
# residue 248) rotation of the line from 210:CA to 240:CA at path node 4. For OR1A1
# this corresponds to bending the TMR5 and TMR6 helices outwards into approximately
# the typical GPCR active configuration.
# Each path node can have an unlimited number of STATE params.
# STATE 3 210 248 25
# Optional alternate PDB, e.g. for receptor activation.
# If uncommented, the specified path node number (in this example 4) will trigger
# loading an alternate model of the protein for docking. This makes it possible to
# dock the ligand first in the protein's default conformational state, and then in
# an alternate conformational state while preserving the conformation of the ligand.
# NODEPDB 4 pdbs/OR1/OR1A1.active.pdb
# Pocket size. If one number is given, it forms the radius of a sphere
# centered around the pocket center. If three numbers are given, they form
# the XYZ radii of an aspect-ratio-distorted spheroid centered around
# the pocket center.
# Default: 10.0.
SIZE 6.0 7.5 5.5
# Optional exclusion zones. Useful for e.g. extracellular loops that in the real world
# protein would flex wildly and not constitute part of the binding pocket.
EXCL 1 57 # Head, TMR1, and CYT1.
# Optional "soft pocket" zones. Defines regions of the protein that are allowed to
# move around during docking, to accommodate ligands of different sizes.
# All regions used here must be defined in the PDB file with REMARK 650 HELIX records.
# SOFT TMR2 TMR4 TMR5 TMR6 TMR7
# Maximum number of poses to output. Default 10.
POSE 10
# Search method.
# Valid choices are BB (best binding) or TS (tumble spheres).
# Best binding looks for the three pairs of ligand-side chain atoms with the best chance
# of forming a non-covalent bond, and attempts to align the ligand accordingly.
# Tumble spheres calculates the imaginary spheres the side chains can flex to inhabit,
# and free-form tumbles the ligand inside this space looking for the most favorable
# superpositions of ligand functional groups with side chain spheres.
# Default is TS.
# SEARCH BB
# Pre-align method.
# If specified, this will do a preliminary dock of the ligand with only the specified
# residues, before going onto the normal whole-protein dock.
# This overrides the SEARCH parameter because pre-align search is mutually exclusive
# to both best-binding and tumble spheres searches.
# PREALIGN 109 203 251 255
# Minimum total binding energy in kJ/mol for output poses.
# Normally this should be either a cutoff threshold for pose screening or a
# small negative number to find all valid poses. Setting this to a positive value
# may cause impossible poses to be output, e.g. ones where atoms are clashing.
ELIM -0.01
# Uncomment this to enable kcal/mol output instead of the default kJ/mol.
# KCAL
# Side chain flexion: active if nonzero. Default: 1.
FLEX 1
# By default, only a few residues will be selected for flexion each pose, in order
# to agree with experimental data that most real world interactions involve three
# or fewer residue flexions:
# https://doi.org/10.1002/(sici)1097-0134(20000515)39:3%3C261::aid-prot90%3E3.0.co;2-4)
# But if a specific residue must flex in order to complete the dock, or must not flex
# in order to exclude non-agonists from the binding pocket, this can be set with
# FLXR and/or STCR parameters, respectively.
# Both residue numbers and Ballesteros-Weinstein numbers are accepted.
# FLXR 104 262 6.48 # Force allow flexion.
# STCR 155 158 4.57 4.60 # Force prevent flexion.
# Optional: if this parameter is uncommented, a differential dock will occur, i.e.
# the total energy of the system will be computed before and after docking the ligand
# and each output value will be given as difference = with ligand minus without ligand.
# Note this increases calculation time as the protein is optimized before docking.
# DIFF
# Optional: If this parameter is uncommented, PrimaryDock will generate up to the
# specified number of water molecules in the binding pocket.
# H2O 10
# Optional: If uncommented, this parameter will activate hydrophobic cohesion, which
# keeps nonpolar groups close together in simulation of an aqueous environment,
# without computing individual water molecules.
# WET
# Number of iterations per path node per pose.
# Higher values equal more precision but decreasing gains and longer processing
# times. Multiples of 10 work best. Default: 50.
ITERS 50
# Optional output file for docking results. Use a file path with filename,
# no spaces. If the file exists, it will be overwritten.
# For best results, include the receptor id (e.g. OR1A1, TAAR5) in the output filename,
# or use the placeholder %p which will auto-replace with the receptor id.
# The %l placeholder stands in for the ligand name auto-replacement.
OUT output/%p_%l.dock
# Optional: Show a progress bar on the screen.
# PROGRESS
# Optional: If docking in a custom PDB that is not one of the included olfactory PDBs,
# the docked PDB can be appended to the .dock file so that the viewer can display the
# entire result including the protein backbone:
# APPENDPROT
# Optional output switches and their defaults.
# PERRES 1 # If nonzero, the per-residue binding energies will be included.
# PERBTYP 1 # If nonzero, the per-interation-type energies will be included.
# ELIMITEM 0.01 # The magnitude limit for itemized (i.e. per-residue and per-type) energies.
# Only energies greater than ELIMITEM or less than -ELIMITEM will be included.
# LIGINTE 1 # If nonzero, the ligand's internal energy will be included.
# OUTBBP 0 # If nonzero, the best-binding pair assignments will be included.
# OUTBBP is only valid if SEARCH BB.
# OUTLPS 0 # If nonzero, the ligand's polar satisfaction will be included.
# OUTPROX 0 # If nonzero, the ligand's proximity to the pocket center will be included.
# OUTPCLSH 0 # If nonzero, the protein's internal clashes will be included.
# OUTMC 0 # If nonzero, the per-residue missed-connection attractions will be included.
# OUTVDWR 0 # If nonzero, the per-residue van der Waals repulsions will be included.
# OUTPDBL 1 # If nonzero, the ligand conformer will be included in the PDB data.
# OUTPDBR 1 # If nonzero, the binding residues, including any flexions if FLEX is enabled,
# will be included in the PDB data.