Development of GROMOS-Compatible Parameter Set for Simulations of Chalcones and Flavonoids

Abstract

Chalcones and flavonoids constitute a large family of plant secondary metabolites that have been explored as a potential source of novel pharmaceutical products. While the simulation of these compounds by molecular dynamics (MD) can be a valuable strategy to assess their conformational properties and so further develop their role in drug discovery, there are no set of force field parameters specifically designed and experimentally validated for their conformational description in condensed phase. So the current work developed a new parameter set for MD simulations of these compounds’ main scaffolds under GROMOS force field. We employed a protocol adjusting the atomic charges and torsional parameters to the respective quantum mechanical derived dipole moments and dihedrals rotational profiles, respectively. Experimental properties of organic liquids were used as references to the calculated values to validate the parameters. Additionally, metadynamics simulations were performed to evaluate the conformational space of complex chalcones and flavonoids, while NOE contacts during simulations were measured and compared to experimental data. Accordingly, the employed protocol allowed us to obtain force field parameters that reproduce well the target data and may be expected to contribute in more accurate computational studies on the biological/therapeutical role of such molecules.

The Lazy Life of Lipid-Linked Oligosaccharides in All Life Domains

“…Finally, we performed conformational analysis on LLOs glycan chains based on the glycosidic dihedral linkages using the same methodology proposed by Arantes et al 21 (Table 4). For better understanding, in the Supporting Information, Figure S4 shows each glycosidic linkage on the LLOs structure with their dihedrals angles φ, ψ and ω highlighted.…”

The Lazy Life of Lipid-Linked Oligosaccharides in All Life Domains

“…Finally, we performed conformational analysis on LLOs glycan chains based on the glycosidic dihedral linkages using the same methodology proposed by Arantes et al 20 (Table 4). For better understanding, in the Supporting Information, Figure S3 shows each glycosidic linkage on the LLOs structure with their dihedrals angles φ, ψ and ω highlighted.…”

“…28,29 Such models had their glycosidic linkage geometries adjusted to the main conformational states for each linkage, based on their relative abundance in the isolated disaccharides in water, as previously described. 21,32,33 Liquid and gas-phase simulations for assessment of thermodynamic properties MD simulations were carried out by using GROMACS 5.0.7 package and physical-chemical properties of organic liquids (density and enthalpy of vaporization) were used as target to validate topology parameters, as previous works of parametrization of small biomolecules 15,16,20 and benchmark of force fields. 17 The geraniol fragment was chosen due to the availability of experimental values of density and enthalpy of vaporization.…”

“…Clusters of conformations that represent the most abundant states on LLOs ensembles were identified based on a previously applied methodology. 20 After identifying these clusters, we submitted the most prevalent structures to PatchDock molecular docking 50 server against their corresponding OST counterparts. Patchdock molecular docking algorithm uses shape complementarity principles with two main steps: i) determining the molecular shape representation to find possible binding geometric patches, and ii) matching of the surface patches between the two molecules.…”

“…QM calculations were carried out using the scan routine combined with a tight convergence criterion, at HF level with the 6-31G* basis set, obtaining the relative energy associated with the rotation of dihedral by increments of 30 • . Analogue MM calculations were performed in GROMACS 5.0.7, using the force field parameter set 53A6, as described in Pol-Fachin et al and Arantes et al,20,28,29 and CHARMM36 30 , for comparison purposes. The MM torsional profile was fitted to the QM profile in Rotational Profiler server,31 providing proper torsional parameters for MM calculations to yield a torsional profile similar to the QM.…”