[gmx-developers] Non Equilibrium alchemy implementation in gromacs

[Piero Procacci]

Dear colleagues

I would like to implement non equilibrium work (NEW) alchemical
methods for solvation and binding free energy calculations in gromacs
The idea is to transpose the ORAC hybrid OpenMP/MPI implementation for
NUMA architectures (which I wrote) to gromacs.  A NEW calculation is
done in two steps:

i) a H-REM simulation where the initial thermodynamic state is 
canonically
sampled (e.g. fully coupled solute/ligand or fully decoupled
solute/ligand)

ii) starting from a representative sample of these canonical 
configurations, a
swarm of fast annihilation or growth NE trajectories (typically few
hundreds) are launched in parallel on the MPI layer. Each trajectory
can be n-threaded on the OpenMP layer.

As I have no experience (as contributor) in the gromacs code, before
embarking in this task I would like to get some info regarding
the current HREM and alchemical implementation in gromacs.

REM question: how does gromacs implement H-REM? namely, are 
topology/parameter
arrays exchanged or the replica exchange concerns (like in ORAC) only 
specific
scaling factors (e.g .factors for torsional scaling, 14 scaling, intra
scaling, inter scaling etc. etc.) with invariant topology throughout
the GE?

ALCHEMY question: when electrostatic of a solute molecule are turned
off no longer interacting with the solvent, are the *intramolecular*
electrostatic interactions also scaled?  namely, if (e.g.)
lambda_q=0.5, do two atomic charges on the solute interact with a 0.25 
scaling
factor?  And if so, how does this get corrected when calcuting solvation
energies?

Thank you in advance for your help

Piero Procacci