While there may be a number of instances where atoms approach each other by less than 5 Å, these interactions represent the majority of significant contacts with respect to the various functionalities of DAN as it is bound to influenza sialidase.
| DAN | Sialidase | SDist. (Å) | SContact Type |
| @O1A | Arg372@NH2 | 2.76 | Ion-ion |
| @O1A | Arg294@NH2 | 3.50 | Ion-ion |
| @O1B | Arg372@NH1 | 2.99 | Ion-ion |
| @O1B | Arg119@NH1 | 2.88 | Ion-ion |
| @O4 | Glu120@OE2 | 3.46 | Ion-dipole |
| @O4 | Asp152@CB | 3.72 | vdW |
| @O6 | Tyr406@OH | 2.89 | Dipole-dipole |
| @O8 | Glu278@OE1 | 2.79 | Ion-dipole |
| @O8 | Glu279@OE2 | 3.59 | Ion-dipole |
| @O9 | Glu278@OE2 | 3.05 | Ion-dipole |
| @O10 | Arg153@NE | 2.71 | Ion-dipole
|
| @C11 | Ile222@CG2 | 3.47 | vdW |
| @C11 | Trp180@CE3 | 3.98 | vdW |
In replacing DAN with 4GDN, several interactions are created and only those to O4 are lost. The following list was prepared with the guanidino group of 4GDN rotated about the dihedral angle C3-C4-N4-C4' to 180 degrees. Other side chains were left in position, though there would undoubtedly be some adaptation to the structure of the new inhibitor.
| 4GDN | Sialidase | Dist. (Å) | Contact Type | Comment |
| @N4 | Glu120@OE2 | 3.46 | Ion-ion | Looks good |
| @N4 | Asp152@OD2 | 3.82 | Ion-ion | Can be adjusted closer |
| @N4B | Trp180@O | 2.34 | Ion-dipole | Close, but can be adjusted |
| @N4B | Arg156@NH1 | 4.56 | Ion-ion | Possibly repulsive! |
| @N4B | Glu120@OE1 | 4.49 | Ion-ion | Could displace Arg156 |
| @N4C | Glu229@OE2 | 3.00 | Ion-ion | Looks Good |
As can be seen from the list above there is one H-bonding oppurtunities and possibly four favorable ion-ion interactions created, with one of the latter likely displacing Arg156 so that no repulsive interactions occur. By comparing binding with the 4-OH derivative, we see that the 105 improvement in binding is the result of 6.82 kcal/mol additional stabilization. Is this reasonable? A hydrogen bond is worth ~2.5 kcal/mol when coupled with an ionic group (like the guanidinium group) and the ion-ion interactions would be expected to be even stronger in a solvent-shielded binding site. Therefore the 6.8 kcal/mol falls short of an expected 10 kcal/mol or more stabilization. Why? Because in the absence of inhibitor, water probably H-bonds with some of the atom groups on affected residues (a 2.8 Å structure would not reveal solvent positions). When inhibitor binds, it displaces those waters, as the enzyme also must displace waters that were formerly H-bonding to the inhibitor. Removing these H-bonds partially detracts from the stabilization that the sialidase-GDN interactions provide.