The AutoTS Input File

The AutoTS input file (name.in) contains keyword-value pairs for defining the parameters of the calculation. Keywords whose values are lists (such as reactant and product structure files) are formatted as comma-separated lists enclosed in square brackets (like a Python list). The keywords are described in the table below.

The AutoTS keywords are separate from Jaguar keywords, which are specified in the &JaguarKeywords section. This section is structured like the sections in a Jaguar input file, beginning with &section and ending with &. It contains &gen section settings for the Jaguar calculations. For information on these keywords, see The gen Section of the Jaguar Input File.

A separate &JaguarKeywords_refinish section can be included to specify Jaguar keywords for AutoTS refinish calculations. When this section is present, the keywords from &JaguarKeywords are not applied to refinish subjobs; only the keywords in &JaguarKeywords_refinish are used. If a keyword is needed in both the main and refinish calculation, it must be specified in both sections. If &JaguarKeywords_refinish is not present, the &JaguarKeywords settings are used for refinish calculations as before.

The following is an example of the contents of a simple input file, which runs AutoTS using the B3LYP-D3/6-31g* level of theory:

charge = 0
multiplicity = 1
reactant = [name-r1.mae, name-r2.mae]
product = [name-p1.mae, name-p2.mae]
free_energy = True
&JaguarKeywords
dftname = b3lyp-d3
basis = 6-31g*
&

The &Constraints Section

The optional &Constraints section keeps selected atoms or internal coordinates fixed during a calculation. Like the other sections, it begins with &Constraints and ends with &. Each line in the section has the form:

title atom1 atom2 ... value

where title is the title of the input reactant or product structure that the constraint applies to, followed by one or more atom indices in that structure. Two kinds of constraint can be specified:

  • Frozen atom — a single atom index and no value. The atom is held fixed during the calculation. For example, reactant1 4 freezes atom 4 of the structure titled reactant1.

  • Internal coordinate constraint — two, three, or four atom indices followed by a target value. Two indices constrain a bond length, three constrain a bond angle, and four constrain a dihedral angle.

A single job can use frozen atoms or internal coordinate constraints, but not both. All input structures must have unique titles when constraints are used.

Constraints With Reaction Complexes

To apply constraints when you supply reaction complexes directly, use complex_structure_constraint as the title instead of a structure title. The atom indices then refer to atoms in the complex. This requires that you supply both a reactant and a product complex with the reactant_complex and product_complex keywords, and set use_complex_inputs to True.

To run AutoTS with frozen atoms:

  1. Generate the reactant (entrance) and product (exit) complexes and save each to its own Maestro file. You can build the complexes in Maestro, or run an initial AutoTS calculation with jobtype = complex_formation_only (see The Complex Formation Only AutoTS Workflow).

  2. Set reactant_complex and product_complex to the complex files, and set use_complex_inputs to True.

  3. Add a &Constraints section that uses the complex_structure_constraint title to freeze the atoms you want to hold fixed.

The following input file freezes atom 4 of the reaction complexes:

reactant = [A.mae, B.mae]
product = [C.mae, D.mae]
reactant_complex = name_reactant_complex.mae
product_complex = name_product_complex.mae
use_complex_inputs = True
charge = 0
multiplicity = 1
&Constraints
complex_structure_constraint 4
&

Table 1. AutoTS input file keywords.

Keyword Type Allowed Values Default Values Description
accept_secondary_afir_path boolean Any True Determines whether or not an afir path is accepted if a secondary reaction has occured.
afir_min_fc integer Any 40 Minimum force constant for AFIR paths.
afir_minima_to_minima boolean Any False Determines whether or not an afir path from minima to minima is done if all methods have failed.
alignment_atoms list of integers Any None The indices of the destination molecule's atoms considered most important for aligning graft molecules with the destination molecule.
allow_disjoint_water_wire boolean Any False Adjust automatic water wire formation analysis to allow water wires that may be disjoint
analytic_hessian boolean Any True Compute an analytic Hessian when performing frequency analysis.
autots_server_hostname string Any None hostname for AutoTS server
autots_server_port integer Any 0 port number for AutoTS server
bond_stretch_fraction real number Any 0.5 Percent change allowed in a stretching bond before it is considered broken when determining if two structure are conformers.
charge integer Any 0 Overall charge of reaction complex.
check_alignment_stability boolean Any True If True, verify that alignment of reactant and product in complexformation is stable.
comparison_type string 
heavy_only
conformers_only
full_rmsd
 conformers_only Method used to determine if two structures are different.
complex_formation string 
random
superimposed
distance-minimization
template
 distance-minimization Methodology used to position molecules and orient torsion angles of rotatable bonds in reactant and product complexes.
conf_search boolean Any False Perform a conformational search after locating transition states.
conf_search_accuracy_level string 
high
low
 high MacroModel conformational search accuracy level. Acceptable values are 0 (low accuracy) and 1 (high accuracy).
conf_search_boltzmann_thresh real number Any 0.005 Threshold on Boltzmann factor used to filter high energy structures prior to frequency evaluation.
conf_search_cluster_conformers boolean Any False Choose conformers for QM optimization from different clusters. This setting attempts to diversify the conformers optimized by the QM method by choosing low energy conformers out of different clusters, grouped by cartesian rmsd, requires a Canvas License.
conf_search_conf_per_clusters integer Any 1 Number of conformations to take from each conformational cluster. See also keyword conf_search_cluster_conformers.
conf_search_constraint_type string 
fixed-internals
fixed-atoms
 fixed-atoms Type of constraint to be used when performing MacroModel based conformational search on transition state geometries
conf_search_energy_window real number Any 10.0 Energy window (kcal/mol) used in conformational search. Only conformers with energies within this value of the minimum energy conformer are kept.
conf_search_file string Any None Conformation search mae file produced by a previous, succesful AutoTS job run with conf_search enabled. To be used with jobtype=energy_correction, conf_search or refinish_only.
conf_search_filter_reactive_optimizations boolean Any True If True, remove any structures which undergo a chemical reaction when performing a Jaguar optimization during the conformational search workflow.
conf_search_gas_phase boolean Any False If True, MacroModel conformational search will be performed in gas phase.
conf_search_intermediates boolean Any True Perform a conformational search on intermediate structures. Requires conf_search to also be set to True.
conf_search_loose_opt_scaling real number Any 10.0 Scaling factor for convergence criterion when doing loose optimization during conformational search stage. This includes constrained optimization used to prepare transition state guess geometries.
conf_search_max_mm_conformers integer Any 200 Maximum number of conformers to request from an initial MM based conformational search.
conf_search_max_qm_conformers integer Any 10 Maximum number of conformers to re-optimize with QM level of theory.
conf_search_metal_centers boolean Any True If False, freeze bond angles where the central atom is a metal.
conf_search_mode string 
complexes
separated
 separated Conformational search can either be applied to reaction complexes or separated molecules.
conf_search_numb_clusters integer Any 0 Number of conformational clusters requested if a value of zero is requested then the number of clusters is determined automatically. See also keyword conf_search_cluster_conformers.
conf_search_products boolean Any True Perform a conformational search on product structures. Requires conf_search to also be set to True.
conf_search_qm_energy_window real number Any 10.0 Energy window (kcal/mol) used in conformational search. Only conformers with energies within this value of the minimum energy conformer are kept after constrained optimization of transition state (TS) geometries and before TS optimization
conf_search_reactants boolean Any True Perform a conformational search on reactant structures. Requires conf_search to also be set to True.
conf_search_ts boolean Any True Perform conformational search on transition state structures. Requires conf_search to also be set to True.
conf_search_ts_vetting_type string 
none
overlap
distance
both
 distance Methodology used when verifying a candidate transition state in the conformational search stage.
constrained_ts_search boolean Any False Freeze the non-reacting part of the molecule when optimizing the transition state. This can enhance the success rate in large flexible systems.
constrained_ts_search_order integer Any 3 Defines the size of the active region when constrained_ts_search=True. The active region is the reaction center plus (order-1)th neighbors. Meaningful values are positive integers.
debug boolean Any False Print extra debugging information.
debug_templates boolean Any False Turn on extra printing for debugging template code.
destination_molecule string Any None The structure title denoting which molecule should be taken as the destination when grafting
die_on_bad_ts_guess_stereochem boolean Any False If the TS guess was found to be likely to lead to incorrect stereoisomeric reactants/products and we were unable to automatically repair the guess, should the calculation proceed. If True, AutoTS will exit if the TS guess could not be repaired.
eliminate_multiple_frequencies boolean Any False Employ techniques to remove multiple imaginary frequencies in transition state optimization.
exit_after_path boolean Any False Exit job after constructing interpolated path.
exit_on_unexpected_rxn boolean Any True Exit the calculation if an unexpected chemical reaction occurs during the initial optimization. This indicates that the input structures are not stable at the requested level of theory.
final_minimize_path boolean Any True Determines whether or not product/reactant realignment is run. Principally for testing atom numbering.
fixed_ts_stereochemistry_label boolean Any False If True, all chiral centers that only occur in the TS are ensured to be labeled R when all active bonds are formed.
flexible_metal_coordination boolean Any False If True, ignore the bonding of metals in the system. Used when only the chemistry of an organic fragment is of interest and coodination of the metal is not.
follow_eigenvector string 
default
active
lowest
non-torsion
stretch
 active Method to choose which eigenvector to follow in a transition state optimization step.
form_rxn_complex boolean Any True Optimally position the geometry of the reactant (entrance) and product (exit) complexes prior to path interpolation. If this is set to False the geometries will be the result of the initial geometry optimization. This parameter is automatically set to False if reactant_complex and product_complex are set and use_complex_inputs is set to True.
free_energy boolean Any False Compute the Gibbs free energy of infinitely separated complexes.
frozen_atoms_rmsd_thresh real number Any 0.3 Threshold for ensuring that frozen atoms are initially aligned
full_path_file string Any None Full path mae file produced by a previous, succesful AutoTS job. To be used with jobtype=energy_correction, jobtype=refinish_only, or jobtype=conf_search.
full_path_separated string Any None Separated full path mae file produced by a previous, succesful AutoTS job. To be used with jobtype=energy_correction, jobtype=refinish_only, or jobtype=conf_search.
generate_raw_path_only boolean Any False If True, do not spline initially generated path
graft_refinement string 
none
forcefield
qm
conformer_search
 forcefield The level of theory for to apply when refining raw graftedreaction complexes before calculating QM energy.
graft_structures string Any None Path to a .mae file containing structures that should be grafted into the reaction.
ignore_chirality_mismatch boolean Any False Ignore errors in chirality (mismatches) outside of the reaction center.If False, AutoTS will exit if chirality mismatches are found.
initial_hessian_type string 
guess
refine
analytic
 refine Type of guess hessian used in transition state optimization.
interpolation string 
distance
internal
cartesian
 distance Coordinate type used to perform reaction path interpolation.
invert_reactive_stereocenters boolean Any False Generate an alternate stereochemical outcome of a stereogenic reaction after locating transition states by inverting the chirality in the reaction center, leaving all other chiral centers uninverted.
irc_path_type string 
irc
mep
 mep Type of path computed by IRC (IRC or MEP)
irc_rms_thresh real number Any 0.02 RMS threshold for sanity check on IRC. This check ensures that the IRC endpoints moved sufficiently far away from the transition state.
irc_ts_vetting_type string 
none
endpoints_match
reaction_occurred
 reaction_occurred Defines how the results of an IRC are used when verifying a candidate transition state. Only applied if require_irc_success=True.
irc_type string 
full_irc
three_point_irc
lqa_irc
skip_irc
 lqa_irc Methods used to perform IRC.
jobtype string 
full
complex_formation_only
path_only
test_renumbering
correct_energies
conf_search
invert_reactive_stereocenters
refinish_only
graft_only
 full Specifies the workflow.
localize_spectators boolean Any True If True, localize spectator molecules near the reaction center. Otherwise, the entire input molecule will be considered for spectator interactions.
loose_opt_scaling real number Any 3.0 Scaling factor for convergence criterion when doing loose optimization. This includes AFIR path construction, initial optimization of reaction complexes and constrained optimization to prepare transition state guess geometries.
max_connections integer Any 10 Maximum number of connections to search for.
max_n_active_bonds integer Any 5 The maximum number of active bonds to consider in a reaction. If a job fails because it could not find a valid active bond set, increasing this may help but the job runtime will be substantially increased.
mm_opt_only boolean Any False Use molecular mechanics (MM) to perform all geometry optimizations.
mm_relax_path boolean Any False Relax path by performing constrained optimizations with MM along interpolated path.
mm_ts_guess_b real number Any 2.0 Value of the parameter b used to compute a guessed TS bond length = b/((b-1)*o + 1), where o is the bond order. The bond order is controled by the parameter mm_ts_guess_order.
mm_ts_guess_order real number Any 0.5 Value of bond order (o) used to compute guess TS bond length = b/((b-1)*o + 1). The parameter b is controlled by mm_ts_guess_b.
multiplicity integer Any 1 Overall spin multiplicity of reaction complex.
neglect_qst_displacement boolean Any True Neglect displacement convergence criterion when optimizing the transition state guess.
optimize_inputs boolean Any True If True, optimize initial complexes. This parameter will be automatically set to False if the parameters reactant_complex and product_complex are set and use_complex_inputs is True.
optimize_outputs boolean Any True If True the final (determined by IRC) minimum energy structures are optimized.
optimize_raw_complexes boolean Any False If True, optimize the initial complexes before computing path. Only for use with Hydrokinetic.
path_dx real number Any 0.2 RMS difference between two structures along the interpolated path. Increasing this value will increase the number of points along the path.
path_npts integer Any 31 Number of points to initially sample the reaction path (before interpolation).
path_type string 
linear
bilinear
quadratic
afir
gsm
 afir Selects a method to compute a reaction path from reactants to products.
product list of strings Any None A list of full paths to Maestro structure files containing individual product molecules.
product_complex string Any None Full path to a Maestro structure file containing the product (exit) complex. If this is defined the initial optimization and positioning of the reaction complexes will be skipped.
pts_guess_with_ts integer Any 0 The number of points around each maximum energy point along the interpolated reaction path used as a transition state guess. If 0, only one point (the maximum energy) is considered. Concretely, if there are n maximum points along the path, then in total n*pts_guess_with_ts of points will be optimized if pts_guess_with is odd, and n*pts_guess_with_ts + 1 of points will be returned if pts_guess_with_ts is even. This setting will cause several TS optimizations to be run in parallel.
qst_endpoints_are_min boolean Any False Use minima instead of posed complexes as QST endpoints.
reactant list of strings Any None A list of full paths to Maestro structure files containing individual reactant molecules.
reactant_complex string Any None Full path to a Maestro structure file containing the reactant (entrance) complex. If this is defined the initial optimization and positioning of the reaction complexes will be skipped.
recompute_input_lewis_structure boolean Any False Recompute the Lewis structure of input structures for the purposes of renumbering complexes.
refinish_basis list of strings Any None Basis sets to run refinement calculations with. Each specified will be run with each refinish_dftname.
refinish_dftname list of strings Any None Levels of theory to run refinement calculations with. Each specified will be run with each refine_basis.
refinish_mode string 
none
energy
 none Selects what type of refinish calculations should be done when refinish_dftname or refinish_basis are set. If a frequency calculation is requested then a geometry optimization will be carried out first.
relax_path boolean Any False Use the relaxed string method (RSM) to improve path.
relax_ts_guess boolean Any True Relax TS guess with constrained optimization before TS optimization.
repair_ts_guess_stereochem boolean Any True If the TS guess was found to be likely to lead to incorrect stereoisomeric reactants/products, we can try and correct the guess automatically. If True, AutoTS will attempt to repair the guess.
require_irc_success boolean Any False If True we require the IRC to succeed before accepting a transition state.
rms_thresh real number Any 0.25 Threshold for RMSD between two structures considered to be different.
skip_complex_free_energy boolean Any False If free energy calculation is requested (free_energy = True) flag that AutoTS should skip calculating the free energies of reactant and product complexes. This saves computational effort if reaction complex free energies are not of interest and was standard prior to release 2026-2.
skip_inf_sep boolean Any False Do not perform calculations to compute the infinitely separated energy.
sn2 boolean Any True Apply an atom numbering correction to SN2 reactions. This correction attempts to invert the chirality of the electrophilic center by renumbering terminal atoms.
sn2_ignore_water boolean Any False Ignore waters when determining atom numbering corrections for SN2 reactions.
spectator_esp string 
jaguar
xtb
 jaguar Methodology used to position spectator molecules in reactant and product complexes.
spectators list of strings Any None A list of paths to Maestro structure files containing individual spectator molecules.
store_autots_data boolean Any True Determines whether or not to send data to a server at the end of the job. Only applicable if AutoTS server hostname and port are given
syn_renumbering boolean Any True Determines whether or not syn renumbering is performed.
temperature_count integer Any 1 The number of temperatures at which reaction free energy is computed if keyword free_energy = True. Sets ntemp Jaguar keyword in all frequency calculations.
temperature_start real number Any 298.15 Initial temperature in Kelvin for computing reaction free energy. Sets the tmpini Jaguar keyword during frequency calculations.
temperature_step real number Any 20.0 Temperature step size (difference between consecutive temperatures) for computing reaction free energy, in K. Sets the tmpstp Jaguar keyword during frequency calculations.
template_database_file string Any None Path to a Maestro structure file containing transition state templates. This file should be prepared by the utility store_reaction_template.
template_order integer Any 1 Order of the subset of atoms used to make constraints on template based transition state guess. Order 1 uses only reaction center atoms. Order 2 uses the reaction center plus nearest neighbors, etc.
ts_acceptance_strictness string 
std
strict
loose
extra_loose
 std Strictness for verification of a candidate transition state.
ts_guess_only boolean Any False Exit job after constructing a transition state guess.
ts_search_type string 
qst
eigenfollow
none
 eigenfollow Algorithm used to perform transition state optimizations.
ts_vet_max_freq real number Any 0.0 Maximum frequency (in cm-1) to consider when vetting transition vectors of an optimized transition state. For example, if this parametert is set to -20.0 only vibrational modes with frequencies less than this value will be considered as possible transition vectors. Note that this setting is independent of the requirement that there is only one negative eigenvalue of the Hessian, this latter requirement is controlled by the setting ts_acceptance_strictness.
ts_vet_with_constraints boolean Any True Project constraints out of Hessian when applying TS vetting. This setting only applies when constrained_ts_search=True. The alternative is to analyze the full Hessian which may contain eigenvectors corresponding to degrees of freedom that were not optimized.
ts_vetting_type string 
none
overlap
distance
both
 both Methodology used when verifying a candidate transition state.
units string 
kcal/mol
ev
 kcal/mol Units used for printing summary tables.
use_complex_inputs boolean Any False If the user has specified files for reactant_complex and product_complex, we will use those complexes rather than generate new ones in the workflow if this variable is set to True. Otherwise, the workflow will ignore those files and generate new complexes.
use_default_templates boolean Any True If keyword template_database_file is not set in the input file, use the user's default set of templates in the user resources directory.
use_mm_ts_guess boolean Any False If True, guess a transition state by performing an MM constrained optimization using intermediate bond distances. These intermediate distances are defined by the keywords mm_ts_guess_b and mm_ts_guess_order.The transition state guess which is optimized is the highest energy point along a path passing through this point.
use_template boolean Any True Use a transition state template if one matches the input reaction type.
use_unrelaxed_ts_on_failure boolean Any False If relaxing the TS guess leads to a reaction or failure and this keyword is set to True, use the unrelaxed TS guess as is. Otherwise, a new TS guess method will be used.
vdw_scale real number Any 1.0 Scales the vdw radii used to position individual molecules when making complexes.
water_wire boolean Any False Analyze inputs and attempt to label to encourage water wire formation
prepare_input_structures boolean Any True Preprocess input structures, converting coordinates from 2D to 3D and adding any missing hydrogens.