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 2008Validation docking method in ArgusLab software.Validation docking in ArgusLab was carriedout for validate the docking method and the variationof grid resolution value in docking simulation withArgusLab. This procedure was used to know howdoes the effect of the variation docking method andgrid resolution value in the result of dockingsimulation with ArgusLab. We compare the dockingmethod in ArgusLab between ArgusDock andGADock method and also the variation of gridresolution (0.1 ; 0.15 ; 0.2 ; 0.25 ; 0.3 ; 0.35 ; 0.4 Ǻ).Both docking methods (ArgusDock and GADock)have different approximation. For ArgusDock, thedocking method use structure and ligandapproximation which is docking mechanism directedto limited position only. Meanwhile, GADock useapproximation which ligand is docking directed to allpossible position in receptor (protein) (9). Thisvalidation prosedure base on the different value ofRMSD (Root Mean Square Deviation) between nativesialic acid ligand and copy sialic acid ligand whichdock into the receptor binding site of hemagglutinin.From this validation, we can get the best dockingmethod and value of grid resolution based on thesmallest value of RMSD. In Tab.2, we can see theresult of validation docking method.Tabel 2 The result of validation docking method inArgusLab 4.RMSD value ofGrid resolutiondocking method(Ǻ)GADock ArgusDock0.1 0.963723 4.1462260.15 1.270897 4.2479860.2 0.614733 4.3979560.25 0.867363 4.2468130.3 1.046308 4.4035480.35 0.711158 4.3913810.4 1.024216 4.458099The docking validation method is valid if the RMSDvalue is not more than 2.0000. From this result, wecan conclude that the smallest RMSD value was0.614733. GADock docking method has smallerRMSD value than ArgusDock. So, GADock is muchbetter used in docking prosedure than ArgusDock.The variation value of grid resolution show that 0.2 Ǻgive the smallest RMSD value in GADock dockingmethod. In this case, we use GADock as dockingmethod and 0.2 Ǻ as the value of grid resolution forrunning docking simulation sialic acid native structureand sialic acid conjugate molecule into the receptorbinding site of protein hemagglutinin.Docking simulation and interaction analysis of sialicacid native structure with protein hemagglutininDocking simulation between sialic acid nativestructure and protein hemagglutinin were carried outwith ArgusLab software. The parameter of calculationwas using parameter data from validation dockingresult. In this case, we use protein hemagglutininVietnam (PDB code:2FK0) which is the host sel comefrom human bird flu case. The result of dockingsimulation (in Fig.5a) show that the best pose ofnative sialic acid structure with predicted bindingenergy value (∆G) -3.5443 kcal/mole. This dockingsimulation create 13 poses of native sialic acidstructure and the best pose indicate that sialic acidgive the best conformation which fit into receptorbinding site of protein hemagglutinin. We also analysethe interaction between ligand native sialic acid andreceptor binding site of hemagglutinin protein.From the Fig.5b, we see that there are 4 hydrogenbonding and 6 hydrophobic interactions which can beformed between sialic acid and hemagglutinin.Hydrogen bonding interactions (red line) are involved2 amino acid residues i.e. Glu190 and His 193.Meanwhile, hydrophobic interctions (blue line) areinvolved 3 amino acid residues, that is Leu 194, Gly228, and Ser 227. Many hydrophobic interactions withprotein hemagglutinin this indicate the sialic acidnative structure can’t get into the active site of proteinhemagglutinin. Hydrogen bonding that is formedbetween sialic acid and hemagglutinin have a weakinteraction and long distance. Overall, from the energyand geometry analysis, the interaction between sialicacid native strcuture and protein hemagglutinin showweak interactions.Docking simulation and interaction analysis of sialicacid conjugate structure with protein hemagglutininFor sialic acid conjugate structure, dockingsimulation used the same parameter data from dockingvalidation parameter that have been done before.The different procedure from docking sialic acidnative structure is treatment of ligand. We subjectedligand as rigid ligand For sialic acid conjugatestructure. Beside that, sialic acid native structure istreated as flexible ligand. This was done in order tosialic acid conjugate molecule can’t change itsconformation. So, the docking simulation was runningwith rigid – rigid docking method. We can see inFig.6a, predicted binding energy value (∆G) fromdocking simulation is about -4.26845 kcal/mole. Thisvalue was less than from docking simulation of sialicacid native structure. From energy analysis, it showthat sialic acid conjugate molecule could bind tightlyin hemagglutinin receptor binding site and also couldshift sialic acid native structure.336