Binding mechanism of RGD and its mimetics to receptor GPIIb/IIIa. A theoretical study

In order to better understand, at a sub-molecular level, the minimal struct ural requirements for the recognition process in the platelet aggregation i nhibitory activity, a series of RGD mimetics were examined as fibrinogen re ceptor antagonists variants. We simulate the electronic interactions betwee n RGD with its biological receptor in terms of smaller molecules. MeCOO- wa s used to mimic the side chain of deprotonated Asp and Meguanidinium group mimicked the side chain of the protonated Arg. Alternative moieties present on the RGD mimetics were also studied in this report. AM1: RHF/3-21G; B3LY P/6-31+ +G** in the gas phase. Also, B3LYP/6-31+ +G** calculations using th e IPCM solvation model were carried out for all the complexes. Our results indicate that high level of theory calculations and the inclusion of solven t effects are crucial in order to obtain satisfactory of accuracy in the el ectronic distributions of these compounds. (C) 2001 Elsevier Science B.V. A ll rights reserved.