are homologous proteinsthat perform opposite functions: FT is an activator of flowering, and TFL1 is a repressor. It was shown beforethat change of a single amino acid (His88) of TFL1 to the corresponding amino acid (Tyr) of FT is enough toconvert the floral repressor to an activator. However, st ructural basis of the functi onal conversion has not beenunderstood. In our molecular dynamics simulations on modified TFL1 proteins, a hydrogen bond present innative TFL1 between the His88 residue and a residue (A sp144) in a neighboring external loop became brokenby change of His88 to Tyr. This breakage induced conf ormational change of the ex ternal loop whose structurewas previously reported to be another key functional de terminant. These findings re veal that the two importantfactors determining the functional specificities of the floral regulators, the key amino acid (His88) and theexternal loop, are correlated, and the key amino acid determines the functional specificity indirectly byaffecting the conformation of the external loop.