Currently, I am performing a Molecular Dynamics simulation in GROMACS, using the OPLS force field. I have a large proteins, of ~650 amino acids that possesses a structural Ca2+ in its core catalytic domain. I performed some tests, and after 100ns the Ca2+ ion jumps from the protein. Thus, I need to bypass this issue and develop some strategy to keep the ion in the protein.
One of the discussed strategies out there is to create a covalent bond between the Ca and the amino acids described to coordinate it. One ramification of this strategy is to use some parameters of the Fe from the heme group. However, I never worked with the OPLS force field before to know how to do it.
Here as some specifics:
1) It needs to be the OPLS force field, because it was described to be more accurate for Ca-containing proteins, and the ligand I will simulate later;
2) Unfortunately, QM analyzes are not an option.
Any ideas are extremely welcome! Thanks.
No artificial covalent bond is needed. Apply a positional restraint to the calcium ion.
Dear Bruno César Feltes
Technically, creating a covalent bond is not a right option. It would be possible that Ca2+ is jumping out due to higher electrostatic repulsion with side chains then it requires a high force constant to keep Ca2+ in the core. Take care of the charge on Ca2+ before applying any positional force. Please browse through the literature on Ca2+ ion parameterization like one belowArticle Calcium ions in aqueous solutions: Accurate force field desc...
As Martin said, you don't need to make the work complex - Just use a simple constraint to take that atom fixed along the simulations...
Another thing is that you should pay is thinking about why that atom jumped out of the protein - maybe it will get back....
Ramin Ekhteiari Salmas Amit Singh Sahrawat Martin Klvana
Thank you all for your ideas. Amit Singh Sahrawat , Thank you for the article, it helped me to fill some knowledge gaps regarding my model and the use of Ca in general.
No action was needed in the end. I performed more analyzes and I found out that the Ca ion never left the protein (Yeah, I know). What happened is that the protein portion containing the Ca touched the box boundaries. I performed a centralization, (taking the Ca into consideration) and it was still outside. It occurred to me that, for some reason, the Ca was probably left there because of some visualization problem. I analyzed the residues that coordinate de Ca ion and found out that it was there, just not appearing in the visualization because the atomic distances were in agreement with the predictions. This is a tricky protein, full of issues that I had to tackle before the simulations, including some prediction problems and Force Field adaptaions. I never used OPLS before and had to deal with a lot manual editing since I will be adding a long hydrocarbon later. Thanks to that, I`ve made this rookie mistake. Thanks again.
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