So that two molecules, either two macromolecules, or a macromolecule and a molecular low-weight drug, can interact one with the other, they must meet and to have a steric and electronic complementarity.
The two molecules must enter in contact one with the other and, for that, drug must be present at the level of its target in a sufficient concentration, which depends on the quantity of drug administered, its capacity to reach the target and finally its affinity and of its specificity for this target. Specificity and affinity result from the structural and electronic complementarities of the concerned molecules.
The endogenous molecule and the drug molecule must have a structural complementarity, as shown in enzymology, the example taken to illustrate this phenomenon is the key / lock adjustment.
The structural complementarity is facilitated by flexibility, i.e. the conformational changes that two molecules can adopt when they approach each other. One speaks in this case of induced conformation.
The electrostatic complementarity facilitates the approach of the drug molecule of its target (receptor, enzyme, channel…) and its binding. There is attraction between the area with strong electron density of a molecule and the area with weak electronic density of another molecule and there is repulsion when the charges are of the same sign.
These interactions between opposite charges are exerted only at very low distances and are moreover modified by the medium which separates them, in particular by the water molecules.
When there are between two molecules both a structural complementarity (hollow/ bump) and an electrostatic complementarity (positive charge/negative charge), they have a very great affinity one for the other. It is what usually occurs between a messenger and a receptor.