TinyArrows (A Tiny Version of EMSL Arrows) - Evolution of Chemical and Materials Computation

We would like thank the DOD SERDP program and the DOE OS OBER EMSL project for providing support that helped with the initial development of EMSL Arrows.

’ EMSL Arrows API’

Tutorial on YouTube (mobile devices)

> Click here to try out Arrows by sending it an email

Are you just learning NWChem and would like to have an easy way to generate input decks, check your output decks against a large database of calculations, perform simple thermochemistry calculations, calculate the NMR and IR spectra of modest size molecule, or just try out NWChem before installing it? EMSL Arrows scientific service can help. A Web API to EMSL Arrows is now available for Alpha testing. Click on this link.

For more information contact Eric Bylaska (eric.bylaska@pnnl.gov)

’ EMSL Arrows API’

The difficulty of simulating the thermodynamic and kinetic properties of new materials is convoluted by the sensitivity of the processes at the macroscopic scale to the atomic scale; the unusual and unexpected bonding behaviors of the materials; the complex extreme temperature and pressure environments likely to be encountered; and the requirements that simulations be as parameter free as possible and extremely reliable. The tools of quantum chemistry and statistical mechanics combined with advanced parallel packages such as NWChem have proved to be very effective and productive. Not surprisingly, programs that implement these types of tools make up a large fraction of DOE OS supercomputer cycles. Despite these hugely successful theoretical developments, reliable calculations of this type require considerable computational effort and often the use of codes with difficult input decks.

The NWChem molecular modeling software implements a robust and diverse set of molecular theories that can estimate the thermodynamics and kinetics of molecules and materials. It arguably has the most capabilities of any molecular modeling code today. The problem with NWChem and other molecular modeling codes is that:

TinyArrows is a software package that combines NWChem, SQL and NOSQL databases, and web applications that simplifies molecular and materials modeling and makes these modeling capabilities easier to use and more accessible to many scientists and engineers and students. TinyArrows is very simple to use. The user just enters chemical reactions into one, of serveral available web applications, and then results are posted back with thermodynamic, reaction pathway (kinetic), spectroscopy, and other results.

TinyArrows parses the input and then searches the database for the compounds in the reactions. If a compound isn’t there, an NWChem calculation is setup and submitted to calculate it. Once the calculation is finished the results are entered into the database and the results are then available to be requested. This whole process is completely automated. To enter different calculation types (e.g. use pspw theory, or pbe0 exchange correlation functional) the SMILES is appended with keyword{options} tags. Examples of inputs are as follows:

C(Cl)(Cl)(Cl)O + C  --> C(Cl)(Cl)Cl + CO 

 C(Cl)(Cl)(Cl)O + C  --> C(Cl)(Cl)Cl + CO ~ theory{pspw}

 C(Cl)(Cl)(Cl)S + C  --> C(Cl)(Cl)Cl + CS

 C(Cl)(Cl)(Cl)S + C  --> C(Cl)(Cl)Cl + CS ~ theory{pm3}

 TNT + 3 benzene --> toluene + 3 nitrobenzene ~ xc{pbe}

The results returned by TinyArrows are a combination of text and graphical output, e.g. entering

 TNT + 3 benzene --> toluene + 3 nitrobenzene ~ xc{pbe}

into TinyArrows produces the following output.

Arrowsoutputimage001b.png

Currently TinyArrows can be used to calculate the following for all NWChem theories:

We envision that as TinyArrows evolves it will be part of future closed cycles of chemical and materials discovery that requires integrated computational and experimental tools combined with materials synthesis.

Installing TinyArrows

Types of Calculations Currently Available and How to Run Them

Molecule

Reaction

NMR

Chemical Reaction Prediction

Generate NWChem Input Decks

Search Molecular Databases

EMSL Arrows API v1.0

Introduction to ESMILES - How to Change Calculation Theories

The combined string, “Molecule_Input keyword1{option1} keyword2{option2} keywordN{optionN}”, is called an “extended smiles” or “esmiles” for short. The Molecule_Input can be specified using a variety of formats including a SMILES string, common names, iupac, kegg numbers, cas, pubchem ids, chemspider ids, and InChI strings. The keyword{option} tags are used to enter different calculation types for a molecule, e.g. use pspw theory, ccsd(t), or pbe0 exchange correlation functional.

The following are examples of esmiles strings:

Plane-Wave DFT calculation using LDA and a cutoff energy=30.0 Ry

c1ccccc1 theory{pspw} xc{lda} basis{30.0 Ry}

MP2 calculation using 6-31G* basis set

CCO theory{mp2} basis{6-31G*}

CCSD(T) calculation of ethanol

CCO theory{ccsd(t)} basis{6-31G*}

Mopac PM3 calculation of caffeine

Caffeine theory{pm3}

Aperiodic plane-wave DFT calculation of triplet cabon tetrachloride

C(Cl)(Cl)(Cl)Cl mult{3} theory{pspw4}

Gas-phase M06-2x/6-31+G* calculation of benzene

benzene theory{dft} xc{m06-2x} solvation_type{none}

Equivalent ESMILES for CCSD(T)/6-31G* calculation of methanol

methyl alcohol theory{ccsd(t)} basis{6-31G*} 

kegg=D02309 theory{ccsd(t)} basis{6-31G*}  

cas=67-56-1 theory{ccsd(t)} basis{6-31G*}  

cid=887 theory{ccsd(t)} basis{6-31G*}  

csid=864 theory{ccsd(t)} basis{6-31G*}  

InChI=1S/CH4O/c1-2/h2H,1H3 theory{ccsd(t)} basis{6-31G*}

The available keywords in and esmiles string are: theory, theory_property, theory_base, basis, basis_property, basis_base, xc, xc_property, xc_base, solvation_type, charge, mult, xyzdata, geometry_generation, and calculation_type.

ESMILES Options - theory{}, theory_property{} and theory_base{}

The default theory used is theory{dft}. The following theories are available:

Examples of calculating the beznene molecule with different DFT theories,

benzene theory{dft}

benzene theory{pspw}

benzene theory{pspw4}

benzene theory{pspw}

MP2 and CCSD(T) theories,

benzene theory{mp2}

benzene theory{ccsd(t)}

and the semiempirical theories.

benzene theory{pm3}

benzene theory{am1}

benzene theory{mindo}

benzene theory{mindo3}

The theory_property{} is an optional keyword used to specify the theory used in an nmr calculation, and theory_base{} is an optional keyword used to specify the theory of the base calculation for an MP2 or CCSD(T) calculation. By default the theory_property and theory_base are defined to be the same as theory{}.

ESMILES Options - basis{}, basis_property{} and basis_base{}

The default basis used is 6-311++G(2d,2p) for the Gaussian DFT, MP2 and CCSD(T) programs. For plane-wave DFT the default basis or cutoff energy is defined to by 50.0 Hartrees or 100.0 Ry.

For Gaussian basis sets any basis set recognized by NWChem can be used, e.g.

CCO basis{6-31G*}

Other common basis sets can be used such as cc-pvdz, 6-311G, 3-21G, 6-31+G*.

For plane-wave basis sets the cutoff energy can changed by just entering the number in Hartrees

CCO theory{pspw] basis{50.0} 

or Rydbergs

CCO theory{pspw} basis{100 Ry}

The basis_property{} is an optional keyword used to specify the basis set used in an nmr calculation, and basis_base{} is an optional keyword used to specify the basis set of the base calculation for an MP2 or CCSD(T) calculation. By default the basis_property and basis_base are defined to be the same as basis{}.

ESMILES Options - xc{}, xc_property{} and xc_base{}

Only the Gaussian and plane-wave DFT programs utilize the xc{} keyword. The default exchange correlation functional used is xc{b3lyp}. The following exchange correlation functions are available with the Gaussian DFT and plane-wave DFT programs.

The xc_property{} is an optional keyword used to specify the exchange correlation potential used in an nmr calculation, and xc_base{} is an optional keyword used to specify the exchange correlation potential of the base calculation for an MP2 or CCSD(T) calculation. By default the xc_property and xc_base are defined to be the same as xc{}.

ESMILES Options - solvation_type{}

The default solvation type is solvation_type{COSMO}. The following solvation types are available with the Gaussian DFT, MP2 and CCSD(T) programs.

The available SMD solvent keywords are given below:

Keyword Name
h2o water (default)
water water (default)
acetacid acetic acid
acetone acetone
acetntrl acetonitrile
acetphen acetophenone
aniline aniline
anisole anisole
benzaldh benzaldehyde
benzene benzene
benzntrl benzonitrile
benzylcl benzyl chloride
brisobut 1-bromo-2-methylpropane
brbenzen bromobenzene
brethane bromoethane
bromform bromoform
broctane 1-bromooctane
brpentan 1-bromopentane
brpropa2 2-bromopropane
brpropan 1-bromopropane
butanal butanal
butacid butanoic acid
butanol 1-butanol
butanol2 2-butanol
butanone butanone
butantrl butanonitrile
butile butyl acetate
nba butylamine
nbutbenz n-butylbenzene
sbutbenz sec-butylbenzene
tbutbenz tert-butylbenzene
cs2 carbon disulfide
carbntet carbon tetrachloride
clbenzen chlorobenzene
secbutcl sec-butyl chloride
chcl3 chloroform
clhexane 1-chlorohexane
clpentan 1-chloropentane
clpropan 1-chloropropane
ocltolue o-chlorotoluene
m-cresol m-cresol
o-cresol o-cresol
cychexan cyclohexane
cychexon cyclohexanone
cycpentn cyclopentane
cycpntol cyclopentanol
cycpnton cyclopentanone
declncis cis-decalin
declntra trans-decalin
declnmix decalin (cis/trans mixture)
decane n-decane
decanol 1-decanol
edb12 1,2-dibromoethane
dibrmetn dibromomethane
butyleth dibutyl ether
odiclbnz o-dichlorobenzene
edc12 1,2-dichloroethane
c12dce cis-dichloroethylene
t12dce trans-dichloroethylene
dcm dichloromethane
ether diethyl ether
et2s diethyl sulfide
dietamin diethylamine
mi diiodomethane
dipe diisopropyl ether
dmds dimethyl disulfide
dmso dimethyl sulfoxide
dma N,N-dimethylacetamide
cisdmchx cis-1,2-dimethylcyclohexane
dmf N,N-dimethylformamide
dmepen24 2,4-dimethylpentane
dmepyr24 2,4-dimethylpyridine
dmepyr26 2,6-dimethylpyridine
dioxane 1,4-dioxane
phoph diphenyl ether
dproamin dipropylamine
dodecan n-dodecane
meg 1,2-ethanediol
etsh ethanethiol
ethanol ethanol
etoac ethyl acetate
etome ethyl formate
eb ethylbenzene
phenetol ethyl phenyl ether
c6h5f fluorobenzene
foctane 1-fluorooctane
formamid formamide
formacid formic acid
heptane n-heptane
heptanol 1-heptanol
heptnon2 2-heptanone
heptnon4 4-heptanone
hexadecn n-hexadecane
hexane n-hexane
hexnacid hexanoic acid
hexanol 1-hexanol
hexanon2 2-hexanone
hexene 1-hexene
hexyne 1-hexyne
c6h5i iodobenzene
iobutane 1-iodobutane
c2h5i iodoethane
iohexdec 1-iodohexadecane
ch3i iodomethane
iopentan 1-iodopentane
iopropan 1-iodopropane
cumene isopropylbenzene
p-cymene p-isopropyltoluene
mesityln mesitylene
methanol methanol
egme 2-methoxyethanol
meacetat methyl acetate
mebnzate methyl benzoate
mebutate methyl butanoate
meformat methyl formate
mibk 4-methyl-2-pentanone
mepropyl methyl propanoate
isobutol 2-methyl-1-propanol
terbutol 2-methyl-2-propanol
nmeaniln N-methylaniline
mecychex methylcyclohexane
nmfmixtr N-methylformamide (E/Z mixture)
isohexan 2-methylpentane
mepyrid2 2-methylpyridine
mepyrid3 3-methylpyridine
mepyrid4 4-methylpyridine
c6h5no2 nitrobenzene
c2h5no2 nitroethane
ch3no2 nitromethane
ntrprop1 1-nitropropane
ntrprop2 2-nitropropane
ontrtolu o-nitrotoluene
nonane n-nonane
nonanol 1-nonanol
nonanone 5-nonanone
octane n-octane
octanol 1-octanol
octanon2 2-octanone
pentdecn n-pentadecane
pentanal pentanal
npentane n-pentane
pentacid pentanoic acid
pentanol 1-pentanol
pentnon2 2-pentanone
pentnon3 3-pentanone
pentene 1-pentene
e2penten E-2-pentene
pentacet pentyl acetate
pentamin pentylamine
pfb perfluorobenzene
benzalcl phenylmethanol
propanal propanal
propacid propanoic acid
propanol 1-propanol
propnol2 2-propanol
propntrl propanonitrile
propenol 2-propen-1-ol
propacet propyl acetate
propamin propylamine
pyridine pyridine
c2cl4 tetrachloroethene
thf tetrahydrofuran
sulfolan tetrahydrothiophene-S,S-dioxide
tetralin tetralin
thiophen thiophene
phsh thiophenol
toluene toluene
tbp tributyl phosphate
tca111 1,1,1-trichloroethane
tca112 1,1,2-trichloroethane
tce trichloroethene
et3n triethylamine
tfe222 2,2,2-trifluoroethanol
tmben124 1,2,4-trimethylbenzene
isoctane 2,2,4-trimethylpentane
undecane n-undecane
m-xylene m-xylene
o-xylene o-xylene
p-xylene p-xylene
xylenemx xylene (mixture)

When a solvent is specified by name, the descriptors for the solvent are based on the Minnesota Solvent Descriptor Database:

Winget, P.; Dolney, D. M.; Giesen, D. J.; Cramer, C. J.; Truhlar, D. G. Minnesota Solvent Descriptor Database. University of Minnesota: Minneapolis, MN, 2010. http://comp.chem.umn.edu/solvation/mnsddb.pdf

ESMILES Reactions - How to Calculate Reaction Energies

The basic input is a chemical reaction where the molecules are specified using smiles strings or esmiles strings (vida infra), e.g.

   C(Cl)(Cl)(Cl)O + C --> C(Cl)(Cl)Cl + CO

Note that the reaction: :reaction keywords have only one “:”, whereas the Arrows keywords use two colons.

The results contain both gas phase and solution phase reaction energies. The default level of theory used in these calculations is b3lyp/6-311++G(2d,2p) and the default solvation model is COSMO. The returned email will contain the following output.

Reaction 1: C(Cl)(Cl)(Cl)O + C --> C(Cl)(Cl)Cl + CO    
- instance 1: 1.00 (Id=6833) + 1.00 (Id=11824) --> 1.00 (Id=6832) + 1.00 (Id=11215)    
- instance 1: 1.00 trichloromethanol + 1.00 methane --> 1.00 chloroform + 1.00 methanol    
- instance 1: 1.00 C1Cl3H1O1 + 1.00 C1H4 --> 1.00 C1Cl3H1 + 1.00 C1H4O1    
- instance 1:   1.00 OC(Cl)(Cl)Cl theory{dft} basis{6-311++G(2d,2p)} xc{b3lyp} solvation_type{COSMO} ^{0} mult{1} nf{?}    
- instance 1: + 1.00 C theory{dft} basis{6-311++G(2d,2p)} xc{b3lyp} solvation_type{COSMO} ^{0} mult{1} nf{0}    
- instance 1:   --> 1.00 C(Cl)(Cl)Cl theory{dft} basis{6-311++G(2d,2p)} xc{b3lyp} solvation_type{COSMO} ^{0} mult{1} nf{?}    
- instance 1:     + 1.00 CO theory{dft} basis{6-311++G(2d,2p)} xc{b3lyp} solvation_type{COSMO} ^{0} mult{1} nf{0}    
- instance 1:        Erxn(gas)       Hrxn(gas)       Grxn(gas) Delta_Solvation        Grxn(aq)    
- instance 1:            8.035           9.580           8.809          -1.991           6.818  -- in kcal/mol    
- instance 1:           33.618          40.084          36.857          -8.332          28.525  -- in kj/mol    
- instance 1:         0.012804        0.015267        0.014038       -0.003173        0.010865  -- in Hartrees

The reaction output for the chemical reaction contains the gas phase reaction energy, gas-phase reaction enthalpy, gas-phase reaction free energy, change in solvation energy, and the solution phase reaction free energy. The energy values are given in kcal/mol, kj/mol, and Hartrees.. Besides the energies the output also provides several rows of information about the calculation:

-       first row: the reaction input parsed  
-       second row: the arrows ids used for the compounds in the reaction  
-       third row: the iupac names of the compounds if available.  If not available the systems will default to using smiles   
                        strings  
-       fourth- rows: the chemical reaction is written using the esmiles notation.  

The esmiles notation contains all the information about the calculations of the compounds. In this example, theory used was dft, basis was 6-311++G(2d,2p), the exchange correlation, the solvation type was cosmo. The charge and multiplicity of the molecules are also given. The value in the nf{} tag contains the number of imaginary frequencies in the vibrational calculation for the molecule.

A variety of other inputs to describe the chemical structure besides smiles can be used, including common names, iupac, kegg numbers, cas, pubchem ids, chemspider ids, and InChI strings. The common names, iupac and InChI strings are entered as replacements to the smiles strings, and the kegg, cas, pubchem, and csid inputs are entered as kegg=value, cas=value, cid=value, csid=value where value is the id. The chemical structure input types can be mixed and matched in the reaction input. The following reaction inputs are all equivalent.

  
trichloromethanol + methane --> chloroform + methyl alcohol
trichloromethanol + C --> chloroform + kegg=D02309
trichloromethanol + C --> chloroform + cas=67-56-1
trichloromethanol + C --> chloroform + cid=887
trichloromethanol + C --> chloroform + csid=864
trichloromethanol + C --> chloroform + InChI=1S/CH4O/c1-2/h2H,1H3

To calculate atomization energies the following input can be used.

 C(Cl)(Cl)(Cl)O  --> [C]  mult{3} + 3 [Cl] mult{2} + [O] mult{3}

MAP Function for Adding Options to Reactions

To calculate a reaction energy using non-default options the following format could be used, e.g.

Arrows::  
  
reaction:   
trichloromethanol theory{pspw} xc{lda} + methane theory{pspw} xc{lda}   
--> chloroform theory{pspw} xc{lda} + methyl alcohol theory{pspw} xc{lda}   
:reaction  
  
::Arrows

in the body of an Arrows email, or just the following single line input in the Web API entry box

 trichloromethanol theory{pspw} xc{lda} + methane theory{pspw} xc{lda}   
 --> chloroform theory{pspw} xc{lda} + methyl alcohol theory{pspw} xc{lda}

Entering ESMILES in this way for reactions is tedius and prone to typos. To simplify this type of input a map function has been added to the reaction input, where the format for the mapping function is to append the reaction with the tilde, “~”, symbol followed by the esmiles options.

trichloromethanol + methane --> chloroform + methyl alcohol ~ theory{pspw} xc{lda}

The map function essentially appends every compound in the reaction by the esmiles options string.This is preferred way to use the map function. However, an alternative format for entering the map function has also been added to the reaction: :reaction block. The format of the block is reaction[esmiles options]: reaction :reaction.

Arrows::  
  
reaction[theory{pspw} xc{lda}]:   
trichloromethanol + methane --> chloroform + methyl alcohol    
:reaction  
  
::Arrows

How to Define the Chemical Structure with XYZ Input

The xyzinput: :xyzinput block is used to enter a chemical structure using xyz coordinates. The label: :label subblock is used to label the xyz structure so that it can be referenced in reaction: :reaction, molecule: :molecule, and nmr: :nmr blocks. The xyz geometry is entered inside the xyzdata: :xyzdata block. The coordinates are assumed to be in Angstroms. The xyz geometry can either contain the number of atoms at the start of the input, e.g.

Arrows::  
 
xyzinput:  
label: amolecule :label  
   xyzdata:  
20  
 
C   0.810772 1.260891 0.224768  
C   -0.445319 0.626551 0.148559  
C   -0.550132 -0.747571 -0.024182  
C   0.598317 -1.510887 -0.051277  
C   1.856720 -0.927387 0.081993  
C   1.951003 0.440481 0.208335  
H   2.736961 -1.550133 0.062422  
H   2.912395 0.927722 0.273890  
O   1.062201 2.575051 0.296009  
C   0.213380 3.557631 -0.323370  
H   -1.520657 -1.209783 -0.105115  
N   -1.712300 1.341956 0.351481  
N   0.485785 -2.966232 -0.210786  
O   -0.636770 -3.441145 -0.327238  
O   1.526277 -3.613525 -0.218259  
O   -2.671572 1.004073 -0.327713  
O   -1.733900 2.198527 1.228109  
H   0.882435 4.349335 -0.647148  
H   -0.510291 3.940088 0.389177  
H   -0.297779 3.136834 -1.188838  
  :xyzdata  
:xyzinput  
 
molecule: label=amolecule xc{m06-2x} :molecule  
 
::Arrows  

r it can be left out, e.g.

Arrows::  
 
xyzinput:  
label: amolecule :label  
   xyzdata:  
C   0.810772 1.260891 0.224768  
C   -0.445319 0.626551 0.148559  
C   -0.550132 -0.747571 -0.024182  
C   0.598317 -1.510887 -0.051277  
C   1.856720 -0.927387 0.081993  
C   1.951003 0.440481 0.208335  
H   2.736961 -1.550133 0.062422  
H   2.912395 0.927722 0.273890  
O   1.062201 2.575051 0.296009  
C   0.213380 3.557631 -0.323370  
H   -1.520657 -1.209783 -0.105115  
N   -1.712300 1.341956 0.351481  
N   0.485785 -2.966232 -0.210786  
O   -0.636770 -3.441145 -0.327238  
O   1.526277 -3.613525 -0.218259  
O   -2.671572 1.004073 -0.327713  
O   -1.733900 2.198527 1.228109  
H   0.882435 4.349335 -0.647148  
H   -0.510291 3.940088 0.389177  
H   -0.297779 3.136834 -1.188838  
  :xyzdata  
:xyzinput  
  
molecule: label=amolecule xc{m06-2x} :molecule
  
::Arrows

How to Calculate NMR Spectra

The nmr: :nmr block is used to energy an NMR calculation

Arrows:: 
nmr: c1ccccc1 basis{6-31G*} solvation_type{None} :nmr
::Arrows

For single line input the esmiles is preceded by the words “nmr for”, e.g.

nmr for c1ccccc1 basis{6-31G*} solvation_type{None}

How to Generate a Table of Reactions

The reactionenumerate: :reactionenumerate block is used to generate a table of reactions in CSV format, which can be copy and pasted into spreadsheets.

Arrows::  
 
reactionenumerate:  
  energytype: grxn(aq) kcal/mol :energytype  
  tablereactions:  
     reaction: TNT + hydroxide --> TNT-2-OH + nitrite :reaction  
     reaction: DNAN + hydroxide --> DNAN-2-OH + nitrite :reaction  
  :tablereactions  
  tablemethods:  
      method: xc{pbe} :method  
      method: xc{b3lyp} :method  
      method: xc{m06-2x} :method  
  :tablemethods  
:reactionenumerate  
  
::Arrows

How to Fetch NWChem Output

The NWChem output can be fetched using the nwoutput: :nwoutput and printnwout: :printnwout blocks. The input for the nwoutput: :nwoutput block is an ESMILES strings, e.g.

Arrows::
nwoutput: TNT theory{pspw} :nwoutput
::Arrows

For single line input the esmiles is preceded by the words “nwoutput for”, e.g.

nwoutput for aspirin theory{pspw}

The input for the printnwout: :printnwout block is an Arrows id, e.g.

Arrows::  
printnwout: 13212 :printnwout
::Arrows

Generate NWChem Input

The Web API can be used to generate an NWChem input deck. For single line input the esmiles is preceded by the words “input deck for”, e.g.

input deck for aspirin

How to Fetch XYZ Geometry

An XYZ geometry can be fetched using the xyzfile: :xyzfile and printxyz: :printxyz blocks. The input for the xyzfile: :xyzfile block is an ESMILES strings, e.g.

Arrows::  
xyzfile: TNT theory{pspw} :xyzfile
::Arrows

The input for the printxyz: :printxyz block is an Arrows id, e.g.

Arrows::  
printxyz: 13212 :printxyz
::Arrows

For single line input the esmiles is preceded by the words “xyz for”, e.g.

xyz for TNT theory{pspw}

Generate a Reaction Path

’ Reaction Path’

As illustrated in the previous section, it is quite common to hypothesize a chemical reaction network that contains multiple branching pathways that are all thermodynamically favorable. As a result of this, relying only on reaction energies can be limiting, and approaches to modeling reaction kinetics, e.g. transition-states and reaction pathways are needed. Unfortunately, these types of calculations involve difficult optimizations that can easily fail. Even in best case scenarios with an expert user running the calculation, this type of calculation will still end up being 10-20 times more expensive than a reaction energy calculation. Modeling reactions in solution is even worse. In addition, transition-states usually contain non-bonding electronic states that are not well described by lower levels of electronic structure theories, and moreover many reactions, even intrinsic one-step reactions, end up having multiple pathways containing multiple barriers. In short, these calculations are time-consuming and difficult, and not surprisingly, automating calculations for transition-states and reaction pathways is an active area of research. Even though transition-state and reaction pathway calculation are not completely automated in Arrows, there are several workflows implemented in Arrows that can be used to perform these types of simulations (see the online Arrows manuals \url{https://nwchemgit.github.io/EMSL_Arrows.html#} or \url{https://ebylaska.github.io/TinyArrows/}).

Reaction path simulations are an example of a molecular simulation that can benefit from the workflow capabilities in Arrows. As a simple example we demonstrate how to calculate the reaction path energies for the following reaction.

 carbon dioxide + [HH] --> carbon monoxide + water

This is a fundamental reaction for catalysis in which methanol is formed by combining the carbon dioxide with hydrogen gas in the presence of a metal catalyst.

1) enter carbon dioxide + [HH]–> carbon monoxide + water into reaction input in the reaction tab of the Expert Periodic and Molecular editor 2) select build reactants from from chemical reaction button 3) select Generate chemical reaction hash button 4) select Search reaction constraings using reaction hash button 5) Enter min_gamma: -6.0 max_gamma: 6.0 and ngamma: 25 6) select the Builder tab then select Unit cell off button 7) select the JSmol to editor button 8) Move to NWChem Input Editor 9) Enter PMF into project name 10) Enter co2toco into mylabel 11) Enter kitchen:/Projects/CCS into curdir0: 12) select NWChem Format button 13) select Add constraint path button 14) Choose machine, ncpu, … options 15) Submit NWChem

    676004        0       no       no              no      aerosol1           ccs  nwchem-71.nw H2C1O2.out00 curdir=kitchen:/Projects/CCS/PMF/pspw-pbe-H2C1O2-co2toco  1634864673.179590