[gmx-developers] Non Equilibrium alchemy implementation in gromacs

[Piero Procacci]

Thanks for your answer

Regarding alchemy:

I now see (oops) on the tutorial for the solvation energy that one "can"
preserve intramolecular interaction while turning off (or on) the
solute while actually one *should* do that for solvation energies!
Otherwise one should do an extra run to compute the free energy change
in turning on (or off) the non bonded intra in the gas-phase.  In any
case it's good that gromacs can handle this and sorry for my silly
question. This point is crucial for NE alchemy since you need to
compute the lambda dependent forces while turning on/off continuously
lambda, and when you do so with PME, you also turn off/on part of the
intramolecular electrostatics in the reciprocal lattice which need to
be added again in the direct lattice (as an erf weighted function of
the intra distances) to keep the full intra interactions. Of course
one does not need to do that dynamically (as it is done in orac). One
can update lambda by discrete small quantities dlambda at regular time
intervals according to a prescribed input protocol. This is what I
intend to do in gromacs sparing me to go inside the direct lattice
force routines.

Regarding REM:

with "topology", I actually meant the parameter set of
the FF. I am not sure to have understood your answer. Does gromacs
*always* exchange coordinates instead of "parameters" or can the code
do both? Exchanging scaling factors (instead of coordinates or the
whole parameters set) would imply close to zero communication overhead
at the MPI (inter-nodes) level allowing to exchange frequently.

Il Giovedì 13/12/2018 14:42 Michael R Shirts ha scritto:
>>     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?
> 
> Currently, the coordinates are exchanged.  It does assume the topology
> is the same, with only parameters changing, though there is quite a
> bit of flexibility in defining parameters (i.e. some atoms off at one
> endpoint, other atoms off at the other endpoint).
> 
>> 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?
> 
> Both area implemented. Not sure what you mean when you say
> "corrected".  Either method gives a valid Hamiltonian that is smoothly
> interpolated between lambda=0 and lambda=1; clearly, they are
> different Hamiltonians with different behaviors, and the equations are
> given in full detail in the manual.
> 
>> The idea is to transpose the ORAC hybrid OpenMP/MPI implementation for
> NUMA architectures (which I wrote) to gromacs.
> 
> This sounds complicated.  I cannot speak to this.  Other people may be 
> able to.
> 
> Best,
> ~~~~~~~~~~~~~~~~
> Michael Shirts
> Associate Professor
> michael.shirts at colorado.edu
> http://www.colorado.edu/lab/shirtsgroup/
> Phone: (303) 735-7860
> Office: JSCBB C123
> Department of Chemical and Biological Engineering
> University of Colorado Boulder
> 
> 
> On 12/13/18, 6:32 AM,
> "gromacs.org_gmx-developers-bounces at maillist.sys.kth.se on behalf of
> Piero Procacci"
> <gromacs.org_gmx-developers-bounces at maillist.sys.kth.se on behalf of
> piero.procacci at unifi.it> wrote:
> 
>     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
>     --
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