Molecular docking of sialic acid and its sialic acid-gadolinium (III ...

M. Khadafi & A. Mutalib Proceeding of The International Seminar on Chemistry 2008 (pp. 333-338)Jatinangor, 30-31 October 2008switch human and avian receptor specificity (Stevenset al., 2006).Gadolinium ion (Gd 3+ ) is very suitable for MRIcontrast agent compound because of paramagneticproperties and stabilization of its chelat. Gadoliniumcomplex molecules are paramagnetic complex that canbe used widely as MRI contrast agent compound.Some factors which cause Gd complex suitable forthis application are Gd 3+ ion have highestparamagnetic properties because of seven unpairelectron in 4f 7 valence shell, have longest electronicrelaxation time, and can form stable chelate that cancoordinate with two water compound (inner-spherecoordination) (Aime et al., 2002). Some example ofGd 3+ complex compounds that have been accepted inclinical study are Gd-DTPA, Gd-BOPTA, Gd-DOTA(Jacques & Desreux, 2002).Recently, avian influenza viruses have beeninfected human as host cell and cause many suspectedpatient bird flu died in large number. For diagnose thesuspected patient bird flu, some hospital are still usinglaboratory prosedure usually performed byimmunochromatographic or immunofluorescentdetection of influenza virus antigens, or reversetranscriptase polymerase chain reaction (RT-PCR)detection of viral nucleic acids in respiratory specimen(Hien et al., 2004). This method is takes a lot of time(4 to 5 days) to have complete diagnose. So, we studythe stabilization and binding affinity of GdDTPAsialic acid conjugate compound throughcomputational chemistry approach for novel MRIcontrast agent compound to diagnose suspectedhuman bird flu by using MRI contrast agent.of grid resolution and docking method in ArgusLab 4.Docking of ligand sialic acid and conjugate moleculeinto the HA (PDB:2FK0) receptor binding site wasperformed with grid resoution and docking methodresult from validation docking method. Bindingenergy (∆G) result was compared and the bestconformation result of both ligands were analyzed thehydrogen bonding and hydrophobic interaction toidentify spesific contact between ligands and HA.Hardware and Software. Cambridgesoft Chem 3D 8was used for molecular modelling. CambridgesoftChem Draw 8 was used for create gadoliniumcomplex structure. Parameter files GdDTPAmolecular mechanic (MM2) calculation wasperformed on Chem 3D 8. Windows Xp Sp 3 wasused as operating system. Arguslab 4.0.1 was used fordocking simulation and analysis interaction.Results and DiscussionModeling of sialic acid – GdDTPA conjugatemoleculeComplex struture of CHx-A”-Gd-DTPAcompound was drawed with chem draw software tocreate the 2 dimension structure of GdDTPA. The 2dimension structure of GdDTPA compound wasexported to 3 dimension structure by using chem 3Dsoftware. The result compound of GdDTPA structurecomplex can be seen in Fig.1.Materials and MethodsModeling of sialic acid and sialic acid – GdDTPAconjugate molecule.The native sialic acid molecule was modeled byconjugate the 3D structure of CHx-A”-Gd-DTPAusing Chem 3D 8 software. Structure of sialic acid andconjugate molecule GdDTPA – sialic acid were doneminimisation energy job using molecular mechanic(MM2) method. Then, conjugate molecule GdDTPA– sialic acid was modified with replaced the electrondonor atom (N atom) of conjugate molecule to dummyatom (Du atom). Both of structure minimisation resultwere calculate the steric energy summary by usingcompute properties job and done the overlay structurebetween those of structures. The parameter resultfrom minimisation i.e. length bond and angel bondwere calculated the root mean square (RMS) value tofind out the deviation value between both structures.Then, validation docking method was carried out bydocking the native sialic acid into receptor bimdingsite (RBS) of HA by using ArgusLab 4 software.Validation method was done to compare the variationFigure 1 The 3D strucure of GdDTPA complexcompound.The native structure of sialic acid was separated fromthe protein HA co – crystallize structure. Then sialicacid structure was conjugated with GdDTPA structurethrough connecting the Nitrogen atom of imine tailGdDTPA structure to Carbon atom 1 (C-1) of sialicacid structure which have been removed the hydroxyltail (-OH) bind to C-1 atom before. The result ofconjugate structure sialic acid – GdDTPA is showedin Fig.2.334