3D-QSAR and docking studies of the stability constants of different guest molecules with beta-cyclodextrin

作者：Ahmadi Parisa; Ghasemi Jahan B^*

来源：Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2014, 79(3-4): 401-413.

DOI：10.1007/s10847-013-0363-5

• beta-Cyclodextrin
• Stability constant
• 3D-QSAR
• GRIND
• GA-PLS
• Docking

This study aims at developing a three dimensional quantitative structure-activity relationship (3D-QSAR) model for predicting complexation of a variety of 126 organic compounds with beta-cyclodextrins (beta-CD). Molecular descriptors were computed using GRid INdependent Descriptors (GRIND) approach. After variable selection via genetic algorithm method, GRIND are correlated with beta-CD complexes stability constants by PLS regression. Kennard-Stone algorithm selected a training dataset comprised of 98 guest molecules. This strategy led to a final QSAR model that showed good internal cross-validation statistics and good predictivity on external data. Those GRIND information which influencing the complexation with beta-CD were also confirmed by the 3D-QSAR and docking studies. All these information revealed that the presence of hydrogen bond acceptor and hydrogen bond donor groups in the molecules caused a more difficult and/or unfavorable complexation reaction with beta-CDs. The size and shape of the molecules as well as hydrogen bonding interactions effects on the stabilities of beta-CDs in inclusion complexes are discussed.

• 出版日期2014-8