A Quick Guide to MOPACMOPAC 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 Superseded by PM7.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-DH 2 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

fixed (0), optimised (1) or considered a reaction coordinate (-1). Coordinates end with a blank line.

Any additional data needed follows after the blank line (e.g. a second coordinate set in a SADDLE or TS calculation, atoms to bind with SETPI, etc..).

You may concatenate several input files.

Next is an example input file for H2+ optimisation:PM7 OPT BONDS AUX GRAPHF GNORM=0.01 + CHARGE=+1 H2+ Optimize geometry and save extra infoH 0.0 1 0.0 1 0.0 1H 1.0 1 0.0 1 0.0 1

FREQUENTLY USED KEYWORDS

SETUP= " file " Read extra keywords from an external file.0SCF Read data and do nothing (used to check input correct-

ness or in combination with RESEQ).1SCF Do a single point SCF calculation and stop (to compute

ground state properties).OPT Optimise the geometry.OPT- X Optimise only atoms of type 'X'.FORCE Compute vibrational frequencies.ESP Compute spin density (e.g. for display in GABEDIT).MULLIK Compute Mulliken's population analysis (useful to as-

sign atomic charges).THERMO Calculate thermodynamic values (entropy, heat capa-

city, internal energy, etc..).UHF Carry out an Unrestricted Hartree-Fock calculation; de-

fault for radicals (systems with odd number of e-).AUX Output an auxiliary file with additional information (e.g.

for use with GABEDIT).BONDS Print final bond matrix (useful to examine bond order).GRAPH Generate a file with graphical information (e.g. for use

in MOLDEN).GRAPHF Generate a formatted file with graphics information (e.g.

for JMOL or MOPETE).GRADIENT S Compute and print all gradients (useful for ten-

sion and Molecular Dynamics calculations).

KEYWORDS USEFUL FOR PROTEIN CALCULATIONS

MOZYME Use localised orbitals to speed up calculations.PDB Input coordinates are in PDB format.CHARGES Calculate the total charge of the system.CHAINS = ( abc.. ) Specify order of chains in a PDB file

(repeat ID for chain fragments).XENO =( Cnn=R,.. ) Specify residue names (chain ID

number = name): e.g., XENO=(A1=MSE,B1=ATP).START_RES=( nC,.. ) Specify start residue numbers n for

incomplete chains C: e.g., START_RES=(13A).CVB =( n1:[+-]n2 ) Add or remove bonds between atoms

n1 and n2: e.g., CVB=(15:-3).SETPI Information on additional pi bonds follows after the co-

ordinates.SITE= ( Cnn([+-0]),.. ) Define ionization state for

specific residues: e.g., SITE=(A123(+),B1(++)).IONIZE Used with ADD-H forces the ionisation of all ionisable

residues in a protein.METAL=( a,b... ) Treat the atoms listed as 100% ionic.GEO-OK Accept the input geometry as is (i.e. do not check it).GEO-REF=" FILENAME " Use geometry in FILENAME as a

reference during optimisation. "SELF" is a special case. The reference must be in MOPAC format.

ADD-H Add all hydrogen atoms to a protein structure (should be optimised afterwards).

OPT-H Optimise positions of hydrogen atoms (used with NOOPT to avoid also optimising all other atoms).

GNORM= n.nn Stop optimisation when the gradient norm drops below n.nn.

MMOK Allow Molecular Mechanics correction for peptide -CO-NH- bonds in protein calculations.

EPS= n.nn Value of the dielectric constant in COSMO implicit solvent calculations (default EPS=78.4).

RSOLV= n.nn Radius of the solvent in COSMO calculations (default RSOLV=1.3).

RESIDUES In the output, save information for each atom indicating which residue it belongs to.

PDBOUT Produce an output file with the coordinates in PDB format. Coordinates may be unsorted.

RESEQ Re-sequence (sort) all atoms by their residue as expec-ted by PDB.

pKa Print pKa for ionisable H attached to O atoms.

KEYWORDS USEFUL FOR SPECIAL SIMULATIONS

THREADS= n Limit to n the threads used in a parallel run.SHUT To stop a long calculation, create a non empty file

with the same name and terminated in ".end".RESTART Restart a previously stopped calculation.EXCITED Compute first excited state of the molecule.

P=n.nn Apply a pressure of n.nn Newton/m3.T = n[H / D / W / M ] Set maximum running time to "n"

seconds/Hours/Days/Weeks/Months.OLDGEO Use last computed geometry (on multiple-job files)

KEYWORDS USEFUL FOR REACTION MODELS

SADDLE Optimise reactants and products to find intermediate transition state.

TS Optimise transition state (used after a SADDLE calcu-lation).

FORCETS Run a FORCE calculation on a TS to check that it is at an inflection point (reactive atom(s) have an imagin-ary, "negative" vibration).

IRC Calculate intrinsic reaction coordinate (compute tra-jectory from TS to reactants/products).

D RC Dynamic reaction coordinate calculation.KINETIC = n.nn Additional kinetic energy (n.nn kcal/mol) for

a DRC calculation.VELOCITY Initial velocity vector for a DRC calculation.POINT= n Number of points to use in a reaction path calculation.

WORKING WITH PROTEINS

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 not in consecutive alphabetic order, or if a chain is discontinuous, use CHAINS to specify them. If there are non-protein molecules or modified amino acids, specify them with XENO.

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 three lines before the PDB file and use the first line to enter your keywords and A DD - H .

Run a calculation with keywords CHARGES RESIDUES. Verify that all residues have the expected number of hydrogen atoms.

Run an intial optimisation on the H atoms only using NOOPT OPT - H GNORM=20.

Check the ionisation states: look for ANION and CATION entries. Verify salt bonds and that, for every ion, there is a counterion nearby. Check potential H-bonds. Ionise "by hand" any needed groups (e.g., phosphates) using SITE. Correct bond orders using SETPI, and eliminate spurious bonds with CVB.

It may be helpful to run a 1SCF calculation to compute properties and a RESEQ calculation to reorder atoms as expected by PDB.

Apply a chemical correction to the original X-ray or NMR struc-ture, running an optimisation using itself as a reference with OPT

GNORM=20 GEO_REF= " SELF " .

Iteratively optimise the structure: run an intial calculation with OPT GNORM=10 CUTOFF=6 T=4W, after it is finished, perform an additional refinement with OPT GNORM=5 CUTOFF=9 T=4W.

Run final 1SCF RESIDUES and RESEQ calculations to check that all, especially the active site and any hetero group(s), is OK.

LOCATING TRANSITION STATES

Know your system in detail. Read all available bibliography.

Prepare datasets representing reactants and products. Spend as much time as needed getting the initial configurations right.

Using GEO_REF =" < products > . MOP " , move the reactants to-wards the products and vice versa. Repeat if needed.

When both structures are close, run a SADDLE calculation.

Refine the transition state with TS, and verify the result with a FORCETS calculation. Repeat if needed.

From a transition state, run IRC or DRC calculations towards the reactants and products to model the full reaction path. MOPAC SITE, DOWNLOADS AND MANUAL

http://openmopac.net/NOTICE: This guide only contains MOPAC key words frequently used in biochemical calculations. Some key words may not be available in older versions of MOPAC. Visit MOPAC web site to consult the manual for de-tailed information, examples and tutorials.

COPYRIGHTSMOPAC: is a trade mark of and by James J. P. Stewart .

CITATION: MOPAC2012, James J. P. Stewart, Stewart Computational Chemistry, Colorado Springs, CO, USA, http://OpenMOPAC.net/ (2012).

THIS DOCUMENT: was written and designed by Jos R. Valverde from the Spanish EMBnet node (CNB/CSIC) and is being distributed by EMBnet's P&PR Committee.

EMBnet the Global Bioinformatics Network is a world-wide support net-work. Many countries have national or local nodes providing training courses and other forms of help for users of bioinformatics software.

Find more information about your nearest node from EMBnet's web site:

http://www.embnet.org/

A Quick Guide To MOPACFirst edition 2014

LICENSE: CC-BY-NC 3.0 http://creativecommons.org/licenses/by-nc/THANKS to James J. P. Stewart, Domenica D'Elia and Terri Attwood.

MOPAC