BMC Genomics 2009, 10(Suppl 3):S19 http://www.biomedcentral.com/1471-2164/10/S3/S19 Figure 4 Docked complexes of PGIP (ribbon representation in blue) and FmPG (space-filling representation in red). A and C show how PvPGIP2 (blue) and GmPGIP3 (blue) respectively, hinder the substrate binding site and block the active site cleft of FmPG (red). The only model of the PvPGIP1-FmPG complex where PvPGIP1 (blue) docks near the active site of FmPG (red) although not blocking it unlike the other two complexes, is shown in B. The marked area shown by the yellow ellipse in B indicates the portion of FmPG that PvPGIP1 has been unable to block. in all the pairs and the other three molecules include PvPGIP1, PvPGIP2 and GmPGIP3. The crystal structure of FmPG (1HG8) used in this study had also been solvated in water and was then subjected to energy minimization followed by molecular dynamics (MD) of 1 ns. Docking studies of FmPG-PvPGIP2 It has been reported that since PvPGIP2 inhibits FmPG, hence one would expect PvPGIP2 to interact with PG by blocking the active site and/or the substrate binding cleft of the fungal enzyme. We obtained top scoring ten docked complexes of PvPGIP2-FmPG from GRAMM-X. One model in the exact expected orientation was selected on the basis of the existing experimental studies (see below). In the docked complex (Figure 4A), PvPGIP2 has covered the active site cleft by hindering the substrate binding site of FmPG. This is evident from the change in Solvent Accessible Surface Area (SASA) (shown in Table 1) for the residues Asp-167, Asp-188, Asp-189, Arg-243, and Lys-245 of FmPG that are known to be located inside the deep cleft and form the putative active site [27]. Functional studies confirm the involvement of these residues in the enzymatic reaction mechanism and or binding to the substrate which is in agreement with the reported mode of competitive inhibition with FmPG [27]. In this model structure, the residues of PvPGIP2 that is known to be functionally important, have shown considerable change in SASA (Table 1), indicating that they play a key role in interaction. Four residues [V (152), S(178), Q(224) and H(271)] out of five that were identified by Leckie et al. [16] as interacting residues of PvPGIP2 are expected to reside in the interacting surface of PvPGIP2 in the PvPGIP2-FmPG complex, inferred on the basis of the considerable change in SASA (Table 1). Docking studies of FmPG-PvPGIP1 Out of the ten potential candidates for models of PvPGIP1-FmPG complex obtained from GRAMM-X, only in one model PvPGIP1 docked to the same face of FmPG as was found in the model for the complex of PvPGIP2-FmPG (Figure 4B). In the rest of the nine models, the PGIP molecule docked to a different face of FmPG indicating a gross inability of these models of PvPGIP1 to block either the substrate binding site or the active site of FmPG. In the selected model, whereas the portion marked with the yellow ellipse is evidently seen to be blocked in the other two complexes, the same is not the case with PvPGIP1. This is in complete agreement with the experimental observation of PvPGIP1 being incapable of inhibiting the PG from Fusarium monili- forme. This model in which FmPG docks to PvPGIP1 at Page 6 of 12 (page number not for citation purposes)