Hypothetical scanning molecular dynamics (HSMD) is a relatively new method for calculating the absolute free energy and entropy. HSMD is extended here for the first time for calculating the absolute free energy of binding, Delta A degrees, as applied to the avidin-biotin complex. With HSMD the ligand is built (more accurately reconstructed) from nothing in solvent and in the protein, in contrast to the commonly used methods where the ligand is annihilated (by thermodynamic integration) in these environments. Therefore, the end-point problem encountered with the latter methods does not exist with HSMD and the need for restraints is avoided. Also, the entropy of the ligand and water in both environments is obtained directly as a byproduct of the simulation. The binding mechanism of biotin to avidin involves a mobile loop that is expected to be in an open conformation in unbound avidin, which is changed to a closed one upon binding, that is, the loop moves to cover biotin in the active site. The contribution of the loop's conformational change to the total free energy of binding is calculated here for the first time. Our result, Delta A degrees = -24.9 +/- 7 covers the experimental value -20.7 kcal/mol within the error bars.