info:eu-repo/semantics/article
Lessons learned about steered molecular dynamics simulations and free energy calculations
Fecha
2019-01Registro en:
Boubeta, Fernando Martín; Contestín García, Rocío María; Lorenzo, Ezequiel Norberto; Boechi, Leonardo; Estrin, Dario Ariel; et al.; Lessons learned about steered molecular dynamics simulations and free energy calculations; Wiley Blackwell Publishing, Inc; Chemical Biology & Drug Design; 93; 6; 1-2019; 1129-1138
1747-0277
CONICET Digital
CONICET
Autor
Boubeta, Fernando Martín
Contestín García, Rocío María
Lorenzo, Ezequiel Norberto
Boechi, Leonardo
Estrin, Dario Ariel
Sued, Raquel Mariela
Arrar, Mehrnoosh
Resumen
The calculation of free energy profiles is central in understanding differential enzymatic activity, for instance, involving chemical reactions that require QM-MM tools, ligand migration, and conformational rearrangements that can be modeled using classical potentials. The use of steered molecular dynamics (sMD) together with the Jarzynski equality is a popular approach in calculating free energy profiles. Here, we first briefly review the application of the Jarzynski equality to sMD simulations, then revisit the so-called stiff-spring approximation and the consequent expectation of Gaussian work distributions and, finally, reiterate the practical utility of the second-order cumulant expansion, as it coincides with the parametric maximum-likelihood estimator in this scenario. We illustrate this procedure using simulations of CO, both in aqueous solution and in a carbon nanotube as a model system for biologically relevant nanoheterogeneous environments. We conclude the use of the second-order cumulant expansion permits the use of faster pulling velocities in sMD simulations, without introducing bias due to large dispersion in the non-equilibrium work distribution.