Hi everyone,I am trying to use AMD to simulate a system in implicit water, with two proteins linked together with a dual headed molecule (PROTAC). The forcefield is ff14SBonlysc + gaff2, igb=5 or 8.
Starting with an equilibrated configuration at the intended temperature (300 K), I am setting up AMD as recommended for explicit water simulations, following the article by Pierce, Salomon-Ferrer and others (Pierce LC, Salomon-Ferrer R, Augusto F de Oliveira C, McCammon JA, Walker RC. Routine Access to Millisecond Time Scale Events with Accelerated Molecular Dynamics. J Chem Theory Comput. 2012;8(9):2997–3002. doi:10.1021/ct300284c).
In brief, I run a short simulation without AMD at constant temperature, and calculate the average potential energy from it. Then I set alphap = natom * 0.16, ethreshp = Epot(average) + alphap, iamd = 1 and start the AMD. The simulation crashes (i.e. energies become huge, etc) after about 40 ns.
The same system runs fine without AMD. I was wondering if a different protocol should be followed for implicit solvent compared to explicit solvent, especially in choosing the alphap and ethreshp parameters.
While calculating alphap (for e.g.), in explicit water systems, we are assigning 0.16 kcal per atom which include all the solvent atoms, while in implicit solvent systems, we are assigning 0.16 kcal to only the solute atoms. Does it lead to an overestimation of alphap and as a result ethreshp? Any insights or suggestions would be highly appreciated.
Thank you very much,Supriyo
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Tue Jun 11 2019 - 12:30:03 PDT
