From: Gumbart, JC (gumbart_at_physics.gatech.edu)
Date: Fri Mar 01 2019 - 23:22:28 CST
My apologies for not also acknowledging the great advice from others - I should have kept reading before replying!
On Mar 2, 2019, at 12:15 AM, Gumbart, JC <gumbart_at_physics.gatech.edu<mailto:gumbart_at_physics.gatech.edu>> wrote:
Adding to Brian’s very helpful advice:
The logic of the CHARMM force field is that if you get interactions with water right, everything else follows (are force field properties really transitive though?), or at least is consistent. I have noticed some improvements when optimizing against interactions with other kinds of molecules, but as you noted, you will break something else in the process.
Ultimately all simulations are approximations; the best way to gain some confidence is to follow the literature where methods you want to use are applied to systems similar to yours (e.g., ABF applied to an ion channel). Even then, there are no guarantees.
On Mar 1, 2019, at 1:13 PM, McGuire, Kelly <mcg05004_at_byui.edu<mailto:mcg05004_at_byui.edu>> wrote:
I have gone through and used the FFTK parameter optimization for new molecules to simulate in NAMD. I have also used Gaussian independently of FFTK to get some parameters. I am trying to get a feel for best parameter optimization practices. Here are the questions I have though:
1) FFTK is mostly used to optimize water-molecule interactions and parameters, correct? But, if the molecule is in a semi-vacuum environment, say an ion channel, that has anywhere from 20-100 water molecules, then the molecule is probably interacting more with the sidechains and a vacuum environment than a bulk water environment. Does the FFTK optimization process do anything for interactions other than water molecules?
2) Partial charges are fixed in MD simulations, so even if I used a program like Gaussian to get good partial charges and then put those in my parameter files, how much can I trust and energy calculation process such as adaptive biasing force free energy profiles? In other words, can my choice of partial charges greatly effect my MD simulations? And, what process do you recommend for optimizing parameters?
3) If QM/MM can be done, is that always the better choice because the interactions will be more accurate for the QM region/region of interest? In the QM region, do partial charges change, or are they still fixed during the simulation?
Kelly L. McGuire
Department of Physiology and Developmental Biology
Brigham Young University
Provo, UT 84602
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