Structural dynamics and binding free energy of neral-cyclodextrins inclusion complexes: molecular dynamics simulation

Abstract

The inclusion complexation of neral, a cis-isomer of citral found in lemon grass (Cymbopogon citratus Stapf), and four different types of cyclodextrin (β-cyclodextrin (βCD), 2,6-dimethyl-βCD (2,6DMβCD), 2,6-dihydroxypropyl-βCD (2,6DHPβCD), and 2-hydroxypropyl-βCD (2HPβCD)) was investigated using molecular docking and molecular dynamics simulation approaches. The simulations show that the neral/CD inclusion complex could be formed in an aqueous solution with a 1:1 ratio. Three possible binding orientations were assessed for the encapsulation of neral (¹neral, ⁷neral, and ^uneral) inside the hydrophobic interior of the host molecule. The ^uneral, in which both aldehyde and alkyl terminals point outward on the secondary rim of the CD, was observed to be the most preferential conformation in all neral/CD complexes. The theoretical calculations of the binding ability of the host–guest inclusion complexes agreed well with the experimental data, thereby supporting that the neral could bind inside the hydrophobic cavity of all CDs with nearly the same potency.

Keywords:

• Cyclodextrin
• neral
• citral
• inclusion
• molecular dynamics simulation

Acknowledgements

The authors gratefully acknowledge the financial supports provided by Chulalongkorn Academic Advancement into its 2nd Century Project (Project [CUAASC] and Chulalongkorn University’s Ratchadapisek Sompot Fund [grant number GCURP59022301]). The authors would like to thank the Structural and Computational Biology Research Group, Special Task Force for Activating Research (STAR), Faculty of Science, Chulalongkorn University. B.N. thanks the Royal Golden Jubilee Ph.D. Program (PHD/0020/2558) and W.P. thanks the Research and Researchers for Industies (MSD59I0066). P. W. is thankful for a short-term visit grant from Chulalongkorn University. T.R. thanks the Thailand Research Fund (RSA5980069 and IRG5780008). N.N. would like to acknowledge the financial support from Mahasarakham University (Fiscal year 2015) and the Center of Excellence for Innovation in Chemistry (PERCH-CIC). The Computer Chemistry Unit Cell and the Vienna Scientific Cluster (VSC-2) are acknowledged for facilities and computing resources.