C7800 Introduction to molecular modelling - seminar -1-
Projects
Project B - Reaction
Petr Kulhanek
kulhanek@chemi.muni.cz
National Center for Biomolecular Research, Faculty of Science
Masaryk University, Kotlářská 2, CZ-61137 Brno
C7800 Introduction to molecular
modelling - seminar
TSM Modeling of molecular structures
C7800 Introduction to molecular modelling - seminar -2Diels-Alder
[4+2]
Cycloaddition Reaction
(Almost) Individual project
➢ Reference manuals
➢ Gaussian (QM calculations)
➢ Nemesis (preparation, visualization)
➢ Infinity (submitting jobs)
C7800 Introduction to molecular modelling - seminar -3How
to process results
I recommend processing the results in the form of a brief protocol, which should fulfill the
following requirements:
• Name and surname, name of the project and date
• For each thematic area:
• Brief summary of the topic, including a reaction scheme, if appropriate
• Software used, including versions
• Results (tables and graphs)
• Discussion of the results according to the assignment
• Used literature (e.g., for experimental values)
C7800 Introduction to molecular modelling - seminar -4-
Tasks
1) Model the butadiene molecule (s-cis and s-trans conformations), ethene and
cyclohexene and optimize their geometry using molecular mechanics.
2) Optimize the geometry of molecules using the quantum chemical method PM3 (this
method does not explicitly state the basis set). Verify that the geometries found are
local minima on the PES. Determine the reaction energy.
3) Select a suitable candidate (reactants or product) for the single coordinate driving
method (SCD). Choose a suitable approximation of the reaction coordinate for the
given candidate to find an estimate of the transition state geometry.
4) Perform SCD using the PM3 method. Display the energy profile along the reaction
coordinate. Visually verify the modeled reaction path.
5) Optimize the geometry of the transition state using the PM3 method. Verify that it is a
first-order saddle point on the PES (put the imaginary frequency value into the
protocol).
6) Optimize the geometry of the pre-reaction complex using the PM3 method. Verify that
this is the local minimum on the PES.
7) Determine the activation energies of the forward and reverse reactions (with respect
to pre-reaction complex and reaction product).
8) Determine the energy of formation of the pre-reaction complex.
9) Compare the calculated energies with the experimental values. Discuss any difference.
C7800 Introduction to molecular modelling - seminar -5Analysis
of reaction transformations
Finding T02 - optional part of the project.
pre-reaction complex productreactantsreactant
transition structure transition structurebarrier-less process
C7800 Introduction to molecular modelling - seminar -6-
Solution
1) Create models for S01, S02, S03, S04. Pre-optimize their geometry using molecular
mechanics (force field MMFF94). Then optimize the geometry by the semiempirical
quantum-chemical method PM3 (the basis set is not explicitly stated). Verify that the
optimized geometries are local minima on the PES.
Data organization
01.S01
01.opt
02.freq
02.S02, 03.S03, 04.S04 (similar to S01)
05.SCD01
06.T01
01.opt
02.freq
07.S05 (similar to S01)
08.SCD02
09.T02
01.opt
02.freq
C7800 Introduction to molecular modelling - seminar -7Solution,
cont.
2) Select the appropriate starting structure and rough reaction coordinate (geometric
parameter) for the SCD in order to find the T01.
3) Load default geometry into project "Build project“. In the "Geometry" tool, select the
selected geometric parameter and create a property from it (button Property).
4) Create an input file for SCD calculation (File->Export Structure as…->Gaussian Input).
Set the calculation parameters (method, charge). Select “Single Coordinate Driving“
and set the driving method (number of steps and their length). Save the input file
(scd.com) and start the calculation.
5) Load the scd.log file into Nemesis (Project: Trajectory, File->Import Trajectory from…>Gaussian->Geometry
1D driving File). Analyze the course of SCD. Use the structure
with the maximum energy value for calculation of T01. Then, select structure with an
estimate of the pre-reaction state to find S05.
6) Use the selected geometry from the SCD to find the transition state. Create an input
file for the calculation (File->Export Structure as…->Gaussian Input). Set the calculation
parameters (method, charge). Choose "Transition Structure Optimization“. Save the
input file (ts.com) and start the calculation.
7) Perform vibration analysis for T01 and S05.
C7800 Introduction to molecular modelling - seminar -8[3,3]-sigmatropic
rearrangament
of chorismate to prefenate
COO
-
OH
O COO
-
O
-
OC
OH
O
COO
-
optional
➢ Reference manuals
➢ Gaussian (QM calculations)
➢ Nemesis (preparation, visualization)
➢ Infinity (submitting jobs)
C7800 Introduction to molecular modelling - seminar -9-
Tasks
1) Model the molecule of chorismate and prefenate and optimize their geometry using
molecular mechanics. Use Avogadro and try to find the global conformational state for
both molecules.
2) Optimize the geometries of the chorismate and prefenate using the quantum chemical
method PM3. Verify that the found geometries are local minima on the PES. Determine
the reaction energy.
3) Select a suitable candidate (reactant or product) for the single coordinate driving
method (SCD). Choose a suitable approximation of the reaction coordinate for the
given candidate to find an estimate of the transition state geometry.
4) Perform SCD using PM3. Display the energy profile along the reaction coordinate.
Visually verify the modeled reaction path.
5) Optimize the geometry of the transition state of the reaction using the PM3 method.
Verify that this is a first-order saddle point on the PES (record the imaginary frequency
value into a protocol).
6) Determine pre-reaction and post-reaction geometries. Compare them with global
conformational states and discuss the difference.
7) Determine the activation energies of the forward and reverse reactions to pre-reaction
and post-reaction state.
8) Compare the calculated energies with the experimental values. Discuss any difference.