[gmx-users] introduction to research on free energies

[asaffarhi at post.tau.ac.il]

Dear Gromacs Users

We would like to introduce a recently published article on calculation  
of relative free energies.

http://www.sciencedirect.com/science/article/pii/S0010465516303411

The article includes a decoupling analysis in which the partition  
functions of the transformed molecules are decomposed into two  
partition functions. It enables to keep dihedral angle terms and  
coupled bond angle terms at the separation point on, independently of  
the function type, also when there is a bond junction at the  
separation point between the shared and unshared submolecules. The  
decoupling analysis is demonstrated in a relative solvation free  
energy calculation of p-Cl and p-CH3 and the calculation is shown to  
be more efficient since less terms are removed. In addition, it is  
proved analytically that when capping the non-bonded potentials (soft  
core technique) the integrated function (in TI) is monotonic (has  
implications for robusteness). It is also shown mathematically that  
when capping the non-bonded potentials and the two molecules are  
simulated separately, the integrated function can be non-steep. It is  
also explained how when the systems have rugged energy landscape they  
can be equilibrated in the same sampling dimension.

Other important references there:

Ref. 34 (33), where it has been suggested to simulate the two  
molecules separately and to cap the potential with accessible energies  
of ~5kcal/mol (page 28, denoted by E_cutoff).

Ref. 35 where it has been suggested to remove terms only of the atoms  
of the unshared submolecules (v1 abstract, v6 Fig. 7) and to cap  
potential terms with accessible energies of 7kcal/mol (v1 Eq. (24)).  
This reference has been split to the article on relative free energies  
and the article on calculation of molecular free energies (Ref 38).

Ref. 38 which is about an exact calculation of molecular free energies  
in a general environment. The calculations include the free energies  
of bond stretching, bond angle, dihedral angle, bond junctions, and  
complex structures. These free energies are also relevant for  
restraints in binding.

Here is the link:
http://iopscience.iop.org/article/10.1088/1367-2630/18/2/023039/meta

Thank you for your attention,
Best regards,
Asaf