Study of the Interaction between Progesterone and β-Cyclodextrin by Electrochemical Techniques and Steered Molecular Dynamics

Abstract

The interaction of progesterone with beta-cyclodextrin (beta-CD) was studied by differential pulse polarography. The aim of the present work was to study the effect of beta-CD on the electrochemical behavior of progesterone in aqueous solution and also to analyze the molecular interactions involved in formation of the inclusion complex. The complex with stoichiometry of 1:1 was thermodynamically characterized. In addition, steered molecular dynamics (SMD) was used to investigate the energetic properties of formation of the inclusion complex along four different pathways (reaction coordinates), considering two possible orientations. From multiple trajectories along these pathways, the potentials of mean force for formation of the beta-CD progesterone inclusion complex were calculated. The energy analysis was in good agreement with the experimental results. In the beta-CD progesterone inclusion complex, a large portion of the steroid skeleton is included in the beta-CD cavity. The lowest energy was found when the D-ring of the guest molecule is located near the secondary hydroxyls of the beta-CD cavity. In the most probable orientation, one intermolecular hydrogen bond is formed between the O of the C-20 keto group of the progesterone and a secondary hydroxyl of the beta-CD.

Steered Molecular Dynamics Simulation in Rational Drug Design

“…Their ability to form complexes with drugs are one type of receptor−ligand interaction studied using simulation. 48 SMD simulations of a cyclodextrin−progesterone complex generated an energy landscape of binding that not only agreed with that previously predicted from experiment but also demonstrated a preferred binding orientation for progesterone. This finding helps future drug design efforts toward more stable bound complexes with increased photostability, suppression of bitterness, and reduction of side effects.…”

Theoretical and Experimental Studies on Inclusion Complexes of Pinostrobin and β-Cyclodextrins

“…In the simulations of the complexes the pulling force reached the maximum value at approximately 500 ps, when the PNS molecule escaped from the nanocavity and the intermolecular interaction between PNS and βCDs (as described in our previous work [ 17 ]) was broken. The results were somewhat in correspondence with the SMD study on progesterone/βCD complex [ 55 ]. Based on the hypothesis that a higher pulling force corresponds to a more favorable binding mode of the guest molecule in the complex, P -PNS preferably interacted with 2,6-DMβCD compared to the interaction of the parental βCD, whilst both orientations of P -PNS and C -PNS were almost equally favorable when binding with 2-HPβCD.…”

Decomplexation and complexation of alkali metal cations by a crown-ether-type podand in dichloromethane: a steered molecular dynamics study

“…SMD has been used to get insights into processes such as the mechanical stability of proteins [31][32][33][34][35][36][37][38], the unfolding and the binding or unbinding of biomolecules [39][40][41][42][43][44][45][46], the transport across membranes [47][48][49][50][51], conformational studies [52] or even the development of new materials [53] or the clarification of enzymatic pathways [54]. In this paper, we report the use of SMD to assess the free energy of decomplexation of the Li ?…”