ONIOM Ca lculation on the Int eraction between T TA Derivatives and Linear–De ndritic Co polymers

The ONIOM (our own n-layered integrat ed molecula r orbital an d molecula r mechanics) hybrid m ethod, which combines a quantu m mechanical (QM) me thod with the molecular mechani cal (MM) method, is one of the powerful m ethods that allow calc ulating lar ge molecula r systems [۱] with the accuracy afforded for smaller molecular systems. T he reliabilit y of the ONIOM metho d has been well established by the Morokuma group and is increasingly adopted as an efficient approac h beneficial to many areas of chemis try [۲]. In t he ONIOM ۲ approach, the system is divided in to two layers, a small part of which, such as t he drug and the reacting amino acids in the binding sit e of an enz yme, is treated at a hig h quantum chemical level, whereas the large surrounding region is mo deled using a lower level of calculations[۳]. A mong the representatives of the no n-nucleosid es reverse transcriptase , NNRTIs, ۲-(۴- (۲,۴-dichlorop henyl)-۱,۲, ۳-thiadiazol-۵-ylthio)-N-acetamide (TTA), has interestin g structure and exhibit significant anti-HIV-۱ activity A s eries of TTA derivatives have be en synthesi zed and ev aluated as potent inhib itors of HIV-۱[۴]. Lin ear–dendritic copolymers containing hyper branched poly (citric acid) and lin ear poly(ethylene glycol) blocks ( PCA–PEG– PCA) are p romising nonmaterial to use in nanomedicin e[۵]. Thus, to investigate their potential application in biological sy tems (espe cially for d rug delivery ), quantum chemical c alculations and a two la yered ONIOM۲ method [۳] were applied to stud y the nature of parti cular interactions between TTA derivatives and the PC A-PEG-PCA copolymers.

کلیدواژه ها:

ONIOM ، Copolymer ، anti-HIV drug ، Interac tion.