Molecular Dynamics Simulations of β-Cyclodextrin−Aziadamantane Complexes in Water

Abstract

Force-field-based atomistic simulations of host-guest supramolecular complexes between beta-cyclodextrin and several aziadamantane derivatives have been analyzed with respect to relative orientation and interaction energies, explicitly considering solvent (water) molecules. For each case, the calculations revealed two stable orientations of the guest within the host that are different in interaction energy. Fluctuation of and correlation between characteristic properties were analyzed. Among other things, it turned out that orientation angle and inclusion depth are clearly correlated. In addition, for the unsubstituted aziadamantane, the enthalpy of complex formation was calculated and compared to experimental results.

Molecular dynamics simulation of configurational properties of complexes between β-cyclodextrin and 2,6-diaziadamantane in water

“…Furthermore, charge groups were used to prevent dipoles from being artificially split when one of the atoms was inside and another was outside the atom-based cut-off. Similar to our findings for 2-aziadamantane [7] the guest entered the host within several hundred picoseconds and then remained within the host.…”

“…Simulation details already have been given in reference [7] but are briefly reproduced in the following for convenience of the reader. First, by use of the Amorphous Cell tool a cubic box (with periodic boundaries in all directions) was prepared which contained one host (7-CyD), one guest (2,6-diaziadamantane) and 600 water molecules, see Scheme 1.…”

“…Module Discover was the molecular dynamics engine making use of COMPASS, which is a class-II force field optimized for the simulation of condensed phases (see references in [7] for parameterization and validation). A cut-off distance of 1.25 nm with a spline switching function (0.3 nm width) was applied for the nonbonding interactions (i.e., for Coulomb and for van der Waals interactions, the latter one being expressed by a 6-9 Lennard-Jones potential).…”

“…Apart from experimental investigations in silico studies are most challenging to predict thermodynamic properties like binding affinities and conformational preferences of host (and guest) molecules as well as relative orientations between the host and the guest [4,5,6]. Recently, we studied the behaviour of complexes between β-cyclodextrin (7-CyD) and several substituted aziadamantanes in water [7]. In the present paper analogous simulations are performed for complexes between 7-CyD and 2,6-diaziadamantane (which contains two diazacyclopropen functionalities) and compared to the (monosubstituted) 2-aziadamantanes.…”

Molecular Modeling Studies of Interaction Between Plasmid DNA (pBR322) and Dendritic Antioxidants

“…There are literatures available regarding the computational and experimental studies of DNA with various drug interactions [20][21][22]. With respect to recently reported computational studies on Cyclodextrin inclusion recognition mostly by molecular dynamics technique, which is based on a systematic, automatic and quasi-flexible docking approach that prevents the influence of the chemist's intuition in the configuration generation [23,24], the inclusion molecular system focused in this work is based on pBR322 as a host ( Figure 1) and a set of dendritic molecules and commonly used antioxidants as guests. In an effort to outline a chart of interaction of DNA-antioxidant energetic, we present here a detailed thermodynamic view of DNA (pBR322) minor-major groove recognition by the G0 dendritic molecules in comparison to commonly used antioxidants (quercetin, vitamins C and E).…”