[gmx-developers] Non Equilibrium alchemy implementation in gromacs

[Michael R Shirts]

>     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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