NAMD QM/MM alchemical free energy change capabilities?

From: Braden Kelly (bkelly08_at_uoguelph.ca)
Date: Mon Nov 26 2018 - 22:07:33 CST

Hello I am interested in calculating hydration free energies of small, whole, organic molecules and want to treat the entire molecule (less than 50 atoms) using QM.

The recent paper "NAMD goes quantum: an integrated suite for hybrid simulations" shows a lot of promise. However I need the free energy change of decoupling the entire molecule. My preferred way is to use an alchemical change where lambda goes from 0 to 1 and/or 1 to 0. Both for the BAR method, which I would also prefer to use. This is not a run of the mill exercise lacking in all the qm/mm software I have looked at and would be a great feature for NAMD to have.

The paper states that "In NAMD, the QMMM interface supports the simulation of many independent QM regions and smooth integration with a collection of enhanced sampling and alchemical methods, including the combination of QMMM approaches with state-of-the-art free energy methods, such as extended adaptive biasing force (eABF). NAMD performs similarly to other QMMM programs in terms of energy conservation (Supplementary Table 1) and allows scalable free energy calculations."

1) can NAMD do alchemical changes where a QM molecule is decoupled from its environment over several lambda windows?

2) failing this, can methods such as pulling a QM molecule from a vacuum into a box of MM water (solvent) molecules be used with PMF calculations to get the hydration (solvation) free energy of inserting a molecule into solution? i.e. https://www.ks.uiuc.edu/Training/Tutorials/namd/ABF/tutorial-abf.pdf The excerpt above says it can do eABF, but in the given context can it?

3) NAMD QM/MM can use PME for long range corrections which is a nice and also advanced feature. Does this work for all QM programs interfaced with NAMD? Other QM/MM software can only do PME for certain built in qm programs, hence why I ask.

Thanks,

Braden Kelly

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