fixed (0), optimised (1) or considered a reaction coordinate (-1).
A Quick Guide to MOPAC Coordinates end with a blank line.
MOPAC is a semi-empirical quantum mechanics (SQM) package,
it has become the QM package of choice in biological calculations.
SQM speeds up quantum mechanics calculations by substituting
many intermediate calculations with their empirically determined
values. As such, it relies on specific parameter sets. MOPAC para-
meter sets are mostly oriented to biochemistry.
MOPAC PARAMETER SETS
PM7 Default. Latest and most accurate. Reported to have prob-
lems with G-C planarity in nucleic acids.
PM7-TS PM7 version to use in transition state reaction
calculations to obtain more accurate barrier heights.
PM6 Good H-bonds, but low accuracy for dipoles and zwit-
terions. Superseded by PM7.
PM6-D3 Add correction for dispersion/correlation.
PM6-DH2 Add correction for dispersion and H-bonds.
PM6-DH+ Also add correction for calculating interaction
and binding energies.
PM6-DH2X DH2 with corrections for halogen-O and halo-
gen-N interactions.
RM1 AM1 re-parametrized for H, C,N, O, P, S, F, Cl, Br and I.
AM1 Used for lanthanides and sparkles.
Generally it is better to use the latest parameter sets (currently
PM7 or PM7-TS for the calculation of transition states). The PM6-
Dx variants are good for computing intermolecular interactions.
Optionally RM1 may be useful for faster calculation of heats of
formation (HoF) and geometry optimisation.
MOPAC INPUT FILE
Keywords to control the calculation are stated in the first line. If
more lines are needed they can be added by including keyword '+'.
If the line is empty, the default is to make an optimisation calcula-
tion using the most modern parameter set. Detailed information on
the parameters can be found at
http://openmopac.net/manual/allkeys.html
Two free format lines follow and are ignored. You can use them to
describe the system.
Atoms and coordinates follow next: they can be in either internal
or cartesian MOPAC coordinate format or in PDB format.
Cartesian coordinate format contains one line per atom consisting
of the atom name, and each of its three X, Y and Z coordinates fol-
lowed by a -1, 0 or 1 to indicate whether that coordinate should be
(repeat ID for chain fragments).
XENO=(Cnn=R,..) Specify residue names (chain ID
Any additional data needed follows after the blank line (e.g. a number = name): e.g., XENO=(A1=MSE,B1=ATP).
second coordinate set in a SADDLE or TS calculation, atoms to START_RES=(nC,..) Specify start residue numbers n for
bind with SETPI, etc..). incomplete chains C: e.g., START_RES=(13A).
You may concatenate several input files. CVB=(n1:[+-]n2) Add or remove bonds between atoms
n1 and n2: e.g., CVB=(15:-3).
Next is an example input file for H2+ optimisation:
SETPI Information on additional π bonds follows after the co-
PM7 OPT BONDS AUX GRAPHF GNORM=0.01 + ordinates.
CHARGE=+1
H2+ SITE=(Cnn([+-0]),..) Define ionization state for
Optimize geometry and save extra info specific residues: e.g., SITE=(A123(+),B1(++)).
H 0.0 1 0.0 1 0.0 1
H 1.0 1 0.0 1 0.0 1 IONIZE Used with ADD-H forces the ionisation of all ionisable
residues in a protein.
FREQUENTLY USED KEYWORDS METAL=(a,b...) Treat the atoms listed as 100% ionic.
SETUP="file" Read extra keywords from an external file. GEO-OK Accept the input geometry as is (i.e. do not check it).
0SCF Read data and do nothing (used to check input correct- GEO-REF="FILENAME" Use geometry in FILENAME as a
ness or in combination with RESEQ). reference during optimisation. "SELF" is a special
1SCF Do a single point SCF calculation and stop (to compute case. The reference must be in MOPAC format.
ground state properties). ADD-H Add all hydrogen atoms to a protein structure (should
OPT Optimise the geometry. be optimised afterwards).
OPT-X Optimise only atoms of type 'X'. OPT-H Optimise positions of hydrogen atoms (used with
FORCE Compute vibrational frequencies. NOOPT to avoid also optimising all other atoms).
ESP Compute spin density (e.g. for display in GABEDIT). GNORM=n.nn Stop optimisation when the gradient norm
drops below n.nn.
MULLIK Compute Mulliken's population analysis (useful to as-
sign atomic charges). MMOK Allow Molecular Mechanics correction for peptide
-CO-NH- bonds in protein calculations.
THERMO Calculate thermodynamic values (entropy, heat capa-
city, internal energy, etc..). EPS= n.nn Value of the dielectric constant in COSMO
implicit solvent calculations (default EPS=78.4).
UHF Carry out an Unrestricted Hartree-Fock calculation; de-
fault for radicals (systems with odd number of e-). RSOLV=n.nn Radius of the solvent in COSMO calculations
(default RSOLV=1.3).
AUX Output an auxiliary file with additional information (e.g.
for use with GABEDIT). RESIDUES In the output, save information for each atom
indicating which residue it belongs to.
BONDS Print final bond matrix (useful to examine bond order).
PDBOUT Produce an output file with the coordinates in PDB
GRAPH Generate a file with graphical information (e.g. for use format. Coordinates may be unsorted.
in MOLDEN).
RESEQ Re-sequence (sort) all atoms by their residue as expec-
GRAPHF Generate a formatted file with graphics information (e.g. ted by PDB.
for JMOL or MOPETE).
pKa Print pKa for ionisable H attached to O atoms.
GRADIENTS Compute and print all gradients (useful for ten-
sion and Molecular Dynamics calculations).
KEYWORDS USEFUL FOR SPECIAL SIMULATIONS
KEYWORDS USEFUL FOR PROTEIN CALCULATIONS
THREADS=n Limit to n the threads used in a parallel run.
MOZYME Use localised orbitals to speed up calculations. SHUT To stop a long calculation, create a non empty file
PDB Input coordinates are in PDB format. with the same name and terminated in ".end".
CHARGES Calculate the total charge of the system. RESTART Restart a previously stopped calculation.
CHAINS=(abc..) Specify order of chains in a PDB file EXCITED Compute first excited state of the molecule.
P=n.nn Apply a pressure of n.nn Newton/m3. GNORM=20 GEO_REF="SELF".
T=n[H/D/W/M] Set maximum running time to "n" Iteratively optimise the structure: run an intial calculation with
seconds/Hours/Days/Weeks/Months. OPT GNORM=10 CUTOFF=6 T=4W, after it is finished, perform
OLDGEO Use last computed geometry (on multiple-job files) an additional refinement with OPT GNORM=5 CUTOFF=9 T=4W.

KEYWORDS USEFUL FOR REACTION MODELS Run final 1SCF RESIDUES and RESEQ calculations to check that
all, especially the active site and any hetero group(s), is OK.
SADDLE Optimise reactants and products to find intermediate
transition state. LOCATING TRANSITION STATES
TS Optimise transition state (used after a SADDLE calcu- Know your system in detail. Read all available bibliography.
lation).
Prepare datasets representing reactants and products. Spend as
FORCETS Run a FORCE calculation on a TS to check that it is at much time as needed getting the initial configurations right.
an inflection point (reactive atom(s) have an imagin-
ary, "negative" vibration). Using GEO_REF="<products>.MOP", move the reactants to-
wards the products and vice versa. Repeat if needed.
IRC Calculate intrinsic reaction coordinate (compute tra-
jectory from TS to reactants/products). When both structures are close, run a SADDLE calculation.
DRC Dynamic reaction coordinate calculation. Refine the transition state with TS, and verify the result with a
KINETIC=n.nn Additional kinetic energy (n.nn kcal/mol) for FORCETS calculation. Repeat if needed.
a DRC calculation.
From a transition state, run IRC or DRC calculations towards the
VELOCITY Initial velocity vector for a DRC calculation. reactants and products to model the full reaction path.
POINT=n Number of points to use in a reaction path calculation.
MOPAC SITE, DOWNLOADS AND MANUAL
WORKING WITH PROTEINS
http://openmopac.net/
Start from a PDB file. Inspect it: if it does not contain the full
chain, use START_RES to specify initial amino acids. If chains are NOTICE: This guide only contains MOPAC key words frequently used in
not in consecutive alphabetic order, or if a chain is discontinuous, biochemical calculations. Some key words may not be available in older
versions of MOPAC. Visit MOPAC web site to consult the manual for de-
use CHAINS to specify them. If there are non-protein molecules or
tailed information, examples and tutorials.
modified amino acids, specify them with XENO.
COPYRIGHTS
Use MOPAC to add all hydrogens: copy the PDB file to a .MOP
file and run MOPAC. If you need to use additional keywords, add MOPAC: is a trade mark of and © by James J. P. Stewart
three lines before the PDB file and use the first line to enter your <MrMOPAC@OpenMOPAC.net>.
keywords and ADD-H. CITATION: MOPAC2012, James J. P. Stewart, Stewart Computational
Run a calculation with keywords CHARGES RESIDUES. Verify Chemistry, Colorado Springs, CO, USA, http://OpenMOPAC.net/ (2012).
that all residues have the expected number of hydrogen atoms. THIS DOCUMENT: was written and designed by José R. Valverde from
the Spanish EMBnet node (CNB/CSIC) and is being distributed by
Run an intial optimisation on the H atoms only using NOOPT EMBnet's P&PR Committee.

MOPAC
OPT-H GNORM=20.
EMBnet the Global Bioinformatics Network is a world-wide support net-
Check the ionisation states: look for ANION and CATION entries. work. Many countries have national or local nodes providing training
Verify salt bonds and that, for every ion, there is a counterion courses and other forms of help for users of bioinformatics software.
nearby. Check potential H-bonds. Ionise "by hand" any needed Find more information about your nearest node from EMBnet's web site:
groups (e.g., phosphates) using SITE. Correct bond orders using
SETPI, and eliminate spurious bonds with CVB. http://www.embnet.org/
It may be helpful to run a 1SCF calculation to compute properties
A Quick Guide To MOPAC
and a RESEQ calculation to reorder atoms as expected by PDB. First edition © 2014
Apply a chemical correction to the original X-ray or NMR struc- LICENSE: CC-BY-NC 3.0 http://creativecommons.org/licenses/by-nc/
ture, running an optimisation using itself as a reference with OPT THANKS to James J. P. Stewart, Domenica D'Elia and Terri Attwood.