Biomolecular recognition is crucial for metabolic and cellular signaling processes. Important contributions to macromolecular interactions comprise directed interactions, conformational flexibility and hydration. In my thesis I investigated several of these factors in order to gain a more comprehensive understanding of said recognition processes. Hydration entropy is important to the energetics of binding, as it is the predominant favorable entropic driving force of complex formation. Both the ligand and the target tend to exhibit decreased conformational flexibility upon binding. In contrast, solvent molecules previously bound to the respective molecular surfaces are liberated to bulk solvent. When weakly bound, these water molecules do not incur a significant enthalpic penalty when displaced. However, they gain in conformational freedom, as their motions are less restricted in bulk solvent, yielding a favorable entropic contribution. Thus, displacing these water molecules yields a net gain in binding free energy and identifying them can provide valuable information in lead optimization campaigns. We derived procedures to evaluate the hydration entropy of water in a localized manner directly from molecular dynamics trajectories.