[gmx-developers] Non Equilibrium alchemy implementation in gromacs

[David van der Spoel]

Den 2018-12-13 kl. 14:31, skrev 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:

For your information, I am not familiar with your method but we have 
worked with some other NE free energy methods and found that 
"traditional" Multistate Bennett Acceptance Ratio (MBAR) is more 
efficient than non-equilibrium methods such as Jarzynsky and Crooks for 
hydration free energies.

https://aip.scitation.org/doi/10.1063/1.5041835

Cheers, David.
> 
> 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


-- 
David van der Spoel, Ph.D., Professor of Biology
Head of Department, Cell & Molecular Biology, Uppsala University.
Box 596, SE-75124 Uppsala, Sweden. Phone: +46184714205.
http://www.icm.uu.se