Computing converged free energy differences between levels of theory via nonequilibrium work methods: Challenges and opportunities.
J Comput Chem
; 38(16): 1376-1388, 2017 06 15.
Article
in En
| MEDLINE
| ID: mdl-28272811
ABSTRACT
We demonstrate that Jarzynski's equation can be used to reliably compute free energy differences between low and high level representations of systems. The need for such a calculation arises when employing the so-called "indirect" approach to free energy simulations with mixed quantum mechanical/molecular mechanical (QM/MM) Hamiltonians; a popular technique for circumventing extensive simulations involving quantum chemical computations. We have applied this methodology to several small and medium sized organic molecules, both in the gas phase and explicit solvent. Test cases include several systems for which the standard approach; that is, free energy perturbation between low and high level description, fails to converge. Finally, we identify three major areas in which the difference between low and high level representations make the calculation of ΔAlowâhigh difficult bond stretching and angle bending, different preferred conformations, and the response of the MM region to the charge distribution of the QM region. © 2016 Wiley Periodicals, Inc.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
J Comput Chem
Journal subject:
QUIMICA
Year:
2017
Type:
Article