I simulated a α-helical protein in implicit solvent using AMBER. However, no matter using the ff99SB or using the ff03 force field, the native secondary structure was lost.
parameters:
igb=5, gbsa=1, cut=16.0, rgbmax=16.0
Successful protein folding is a rare success. Force fields are not very good.
Implicit models make a lot of approximations and assumptions. Often, you will observe strange behavior in an implicit simulation while the protein behaves normally in an explicit solvent. Defects in force fields can contribute to this behavior (though the two parameter sets you list should not intrinsically lead to helical destabilization), the implicit model itself may be to blame. I presume the protein is stable in a normal explicit environment with the same force fields?
Hi, Justin Lemkul. Can you tell me which two parameter sets are not good for helical structures? Or do you have any suggestions for the simulation in implicit solvent? Thank you.
To save the helical structures you can try Amber94 and Amber99. They give a strong preference for helical structures.
Amber94 is artificially strong; you get the "right" answer for the wrong reason. Amber99 has some bias, but it's not as bad. The original force fields chosen (ff99sb and ff03) are reasonable choices. I would suggest to the OP to run the simulation in explicit solvent to verify if the structure holds together there. If it does, then the problem is with the use of the implicit environment. If it does not, then the force field is indeed to blame, but I would not revert back to ancient force fields with widely known problems.
Thank you very much. I performed the simulation in explicit solvent using ff03 force field and the native structure has been well conserved. Therefore, I think there should be some problems when using the implicit solvent. Maybe the results in implicit solvent is not reliable.
In explicit solvent the simulation is 100ns, but the protein loses some native secondary structures in no more than 20 ns.
The fact that in the implicit water protein folds 2-3 orders faster. Therefore, to say anything about the stability in the explicit water we need very long calculations.
On the other hand, most of the proteins are not stable in both cases. So if your task allows it, I would artificially stabilize the structure, such as picking up the appropriate version of the force field.
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