FEARCF a multidimensional free energy method for investigating conformational landscapes and chemical reaction mechanisms

Abstract

The development and implementation of a computational method able to produce free energies in multiple dimensions, descriptively named the free energies from adaptive reaction coordinate forces (FEARCF) method is described in this paper. While the method can be used to calculate free energies of association, conformation and reactivity here it is shown in the context of chemical reaction landscapes. A reaction free energy surface for the Claisen rearrangement of chorismate to prephenate is used as an illustration of the method's efficient convergence. FEARCF simulations are shown to achieve flat histograms for complex multidimensional free energy volumes. The sampling efficiency by which it produces multidimensional free energies is demonstrated on the complex puckering of a pyranose ring, that is described by a three dimensional W( 1 ,  2 ,  3 ) potential of mean force. free energy calculations, reaction dynamics, reaction surfaces, multidimensional free energy surfaces

Ring Puckering Landscapes of Glycosaminoglycan-Related Monosaccharides from Molecular Dynamics Simulations

“…These boost coordinates were chosen due to their successful previous use in Hamiltonian replica exchange studies of uronic acid puckering by Babin and Sagui. 14 It is however noted that other puckering coordinates, such as Hill-Reilly 36 or Cremer-Pople angles, 37 have also been found to be effective in previous enhanced sampling studies 10,11 and could equally have been employed in the current work. On completing the unbiased MD equilibration process, eight independent trajectories were propagated over a 1 ns period.…”

Producing DFT/MM enzyme reaction trajectories from SCC‐DFTB/MM driving forces to probe the underlying electronics of a glycosyltransferase reaction

“…The are computed from these ensembles which allows the calculation of the potential of mean force (PMF) for the chemical reaction. The for the reaction is gained from negative of the PMF which is computed using the FEARCF method . Here, several FEARCF iterations, where in each iteration the negative of the PMF gradient from the previous iteration is applied to the reaction coordinate as a perturbing force, eventually converges to the .…”

“…The FES l n ð Þ for the reaction is gained from negative of the PMF which is computed using the FEARCF method. [1,21,22] Here, several FEARCF iterations, where in each iteration the negative of the PMF gradient from the previous iteration is applied to the reaction coordinate as a perturbing force, eventually converges to the FES l n ð Þ. At a higher level of theory external weighting functions are applied to n a , that are derived from FES l n ð Þ, to advance the reaction trajectory from the reactants (R) across the transition state (TS) separation barrier to the products (P).…”

From China to the world: Science China Chemistry celebrates the International Year of Chemistry

“…Development of sampling techniques is of intense interest for free energy evaluation. Kevin Naidoo of South Africa described the free energies from adaptive reaction coordinate forces (FEARCF) as a computational method (Figure 9) [28]. Ye Mei, John Z. H. Zhang and coworkers presented their com- …”