Hi,
I am doing MD simulation of a polymer in TIP3P water now. The monomer has a 7membered ring. With AMBERTOOLS15, I used PARAMFIT to get a set of force field for it. I used TLEAP to combine monomers to a polymer and pack it with TIP3P water.
After running for 20ns at 300K (NPT), I extracted some fragments from the trajectory file. These fragments were all monomer with missing terminals. I added hydrogen atoms to makeup the terminals. And then I used Gaussian09 to do SP and OPT with MP2/6-31G* to see the potential difference.
The results showed the conformation extracted from MD simulation had much higher potential than its optimized conformation. I had 24 conformations. The biggest potential difference was 66kcal/mol. The smallest potential difference was 35kcal/mol.
I know MD simulation could overcome small energy barrier, but the potential difference was too big. Is this condition normal?
Thanks,
Xiaoquan.
Hi Xiaoquan,
I do not completely understand your question. You take a structure (or a part of one) from an MD simulation an carry out a single point calculation with Gaussian on this structure. Then You relax this structure to the next (local) geometry minimum and compare the total Energies. And wonder where the total energy (potential?) difference might arise from. Right?
If this is the question, I would answer:
Your structure from the MD simulation is a snapshot of a dynamic trajectory at room temperature in a dielectric solvent (water) and not a relaxed geometry in vacuum as in the Gaussian simulation. Relaxing the structure in vacuum with the OPT key word will give another (most likely less polar) local energy minimum structure. Additionally the force-field You use produces geometries (dihedrals, bond-lengths, angles) according to its parametrization and these geometries can be (will be) far from the relaxed geometries in Gaussian (just compare the bonding distances). Besides, if You carry out your relaxation (OPT) in Gaussian in implicit or explicit solvent or if you take another method (DFT, MP4, CC, ....) of if You change Your basis set You will again find other (local) minimum structures and hence other total energies. The local minimun structures in gaussian are always only structures of minimal energy for a given basis set and computation method.
I am not really aware of what you want to calculate with a post simulation optimization of Your structures, but any optimization in Gaussian with the OPT key-word will "destroy" the dynamicall structure you generated in the MD simulation.
Is this condition normal? Yes it is (if I understood your question right)
Regards Sebastian
Thanks, Sebastain,
That's exactly what I mean. My advisor asked me to do this. She thought the potential difference should not be very big. I am trying to find a way to explain this but do not know where to start.
I will search more about dynamics structures. This is a good key word.
Hi Xiaoquan,
if you want to compare the individual conformations of these 7membered ring-struktures, then I would stay in the MD wolrd and give a first try using amber:
This should give you well equilibrated structures and you can look at the corresponding energy output of amber. Then you should proceed to robust simulations:
To get real stability-differences of the individual monomers in solution no need to take out Free Energy calculations. Amber is capable of computing for example Thermodynamic Integration Simulations, Free Energy Perturbation, Umbrella Sampling, etc. You get Free Energy contributions according to solvation and conformation. I think this is what you want. You find examples in the Amber tutorials, I have added a link. Some Thermodynamic Integration application you find in my doctor-thesis. The introdiction is in german, but the corresponding papers are at the end of the file in english. You could get a TI scheme to transfer one structure into the other or even develope schemes to probe your whole polymer containing specifically build monomers.
I think a post procession of your MD simulations with quantum mechanical methods to answer such questions is rather complicated.
Regards Sebastian
http://ambermd.org/tutorials/#free_energies
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