Application

Computational Approaches for Bio-markers Design:
Application: Modeling the solvatochromism in p-nitro anilene
• (i) How to create coordinates for a molecule (use MOLDEN)
• (ii) To get the optimized geometry and compute charges in a particular solvent (use
GAUSSIAN)
• (iii) Prepare the solute-solvent initial configuration (use Ambertools)
• (iv) Run MD for the solute-solvent system (use AMBER12) with Rigid and flexible
solute
• (v) Analyze the solute-solvent structure and prepare QM/MM input files
• (vi) Run QM/MM calculations to compute OPA and TPA properties (use DALTON).
Let us refer the results for rigid solute as (vi-a) and for the flexible solute as (vi-b)
• (vii) Use trajectory from hybrid QM/MM MD and compute the properties.
In this excercise, we will model the solvatohromic property of p-nitro anilene.
Solvatochromism refers to the solvent induced changes in the optical properties
of a molecule. A positive solvatochromism refers to red shift in the absorption
spectra due to inrease in the polarity of microenvironment and the negative solvatochromism refers to blue shift. Below, we list the absorption maximum obtained
for PNA and other structurally similar compounds and this has to be reproduced
from computational modeling.
Table 1. Absorption maximum (nm) of PNA in different solvents.
Solute
PNA
1
Dichloro methane
349
in water
380
Problem-1 : Optimization of p-nitroanilene in gas phase,
dichloromethane and water solvents
• Draw the molecular structure of p-nitro aniline (shown in Figure below) using molden[1].
• optimize the molecular geometry in gas phase, dichloromethane and water solvents (use
option POP=CHELPG to print the ESP charges for PNA) [2]
• Check wether the geometry corresponds to minimum
• Take a look into charges and dipole moments. What do you observe?
• Any interesting observation in the normal modes with dependence on the solvent? There
are connections between your observation and the working mechanism for various IR and
Raman probes.
Figure 1: p-nitro aniline
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Problem-2 : One photon absorption spectra calculations using static approach
• Carry out TD-DFT calculations for PNA in three different environment (as in problem-1).
Account for the solvent effect using polarizable continuum model.
• Try to find out which is the optimal basis set. Use the experimental absorption maximum
for PNA in specific environment as the reference data.
• Do calculations using B3LYP and CAM-B3LYP functional compare with experimental
results.
• Add explicit solvents (for the water solvent) and do the step above. Are the results better?
• The solvent dependent absorption maximum is the property that is exploited in the design
of various optical probes.
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Problem-3 : Dynamic approach- Molecular dynamics
simulations for PNA in solvents
• Use Antechamber to prepare the .prepi, .frcmod and .pdb (or .mol) files for the solute
and solvents[3]
• Use tleap/xleap to prepare the solue-solvent configuration[3]
• Carry out minimization, finite temperature and pressure calculations (at room temperature and 1 atm pressure)[4]
• Use two different molecular models for PNA (rigid and flexible molecular model)[4]
• How long we need to run the simulation? Use the script () to check the convergene of
density and energetics.
antechamber -fi gout -fo prepi -i input.gout -o output.prepi -c esp -j 4 -at gaff
antechamber -fi gout -fo pdb -i input.gout -o output.pdb
parmchk -i output.prepi -o output.frcmod -f prepi
LoadAmberPrep I.prepin //load prep input file
LoadAmberParams I.frcmod //load additional force field
LoadAmberParams parm99.dat //load parm99 force field
LoadAmberParams gaff.dat //load gaff force field
sys = loadpdb C.pdb //load pdb file
solvatebox sys TIP3PBOX sys 20.0 //add solvent molecules, suppose add a box water
saveAmberParm sys C.prmtop C.prmcrd
quit
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Problem-4 : Preparing QM/MM input files
• Prepare mol conf.usr file from the trajectory.
• Prepare the QM/MM input files using whirlpool program. (for three cases trajectory
corresponding to rigid body MD, flexible body MD and ab inition QM/MM MD)
• Compute one photon absorption property for all three cases and tabulate the values and
compare to the results obtained from static case and write a report about which approach
is optimal.
gfortran qmmm.f90
./a.out
cp fort.121 mol_confs.usr
python whirlpool.py
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References
1. http://www.cmbi.ru.nl/molden/molden.html
2. http://www.cup.uni-muenchen.de/ch/compchem/pop/chelpg.html
3. http://ambermd.org/antechamber/ac.html
4. http://ambermd.org/tutorials/basic/tutorial1/section2.htm
5. http://ringo.ams.sunysb.edu/index.php/2012 AMBER Tutorial with Biotin and Streptavidin
6. http://enzyme.fbb.msu.ru/Tutorials/

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