I use GROMAC 4.5.5 to carry out MD for 40ns with protein-ligand complex in water box. I 'm currently calculate free binding energy of ligand and protein but I have no idea to how to do calculation. Do I need to run more MD and can use g_energy to calculate ennergy?
Please refer this paper to analyze your results.
http://pubs.acs.org/doi/abs/10.1021/ci500020m
This tool has been created by JNU and OSDD team india and working good for MMPBSA calculations.
Ms Shipra Gupta. I tried to install g_mmpbsa to gromac but i cannot locate APBS library directory for g_mmpbsa. Are there any alternative way to calculate free binding energy (ie. manually...)
There are numerous ways to calculate binding free energy. PMF, thermodynamic integration, BAR, FEP, etc.
Thank you for very much for the suggestion, I tried FEP method but it didn't work in my case since protein's binding pocket is open to allow water molecules get into. i would rather try PMF.
Regarding installation of g_mmpbsa, please follow the steps of APBS installation as provided in g_mmpbsa site. To install APBS in "/opt/apbs" you will need to be as a super-user (su or sudo).
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tar -zxvf apbs-1.3-source.tar.gz
cd apbs-1.3-source
./configure --prefix=/opt/apbs
make
make install
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Library files will be installed in "/opt/apbs/lib" directory.
Dear colleague,
There are two methods in Gromacs you can use to calculate the energy of ligand binding protein. One is in the LIE, which you need to do two simulations, one with the ligand in the bound state (complex) and another, under the same thermodynamic conditions with the free ligand (in water). Use G_lie to calculate the free energy.
Another method is the thermodynamic cycle, this takes longer than the first this reach better results because need search all space of configurations.
Hope this helps!
Dear Elias Santos,
Your comment really help me in calculating free binding energy. I 'll try with LIE method.
Thank you very much!
Be advised that LIE does not include entropic contributions; it *estimates* the free energy based solely on nonbonded interaction energies. For some force fields, this estimate can be very poor. If you need a more accurate binding free energy, you need to do more intensive calculations.
It is true, depending on the force field used LIE's method can not be a good option. Because it does not search the entire space of configurations and it use the contribuitions eletrostatic and van der Waals of short range. Remember that's an estimate, but it is valid if you know the experimental value. However, I finding good results.
I strongly suggest that you evaluate your needs with respect to accuracy of the results and the time available. Thus, you can choose the best method.
I have run MD simulation for 4 individual system with 4 different ligand in complex with the same protein. What I would like to do next is calculate the free binding energy for 4 system. I refer MM/PBSA method but i don't know how to do it,
I tried FEP but it is improper in my case and if I try with PMF method, do I have to run from the begining.
I am new in these methods, any detail suggestions will help me a lot.
You can use AmberTools. It's free and very straightforward. You just need to convert the trajectories to a format that could be understood by Amber. I'm not sure if this is possible or not.
You can use AmberTools. It's free and very straightforward. You just need to convert the trajectories to a format that could be understood by Amber. I'm not sure if this is possible or not.
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