The Arabidopsis pyrabactin resistant 1 (PYR1)-like family of proteins (PYLs) are receptors of abscisic acid (ABA), an essential small signaling molecule in plants. Here, we report a comparative molecular dynamics (MD) study on two PYL members, PYR1 and PYL10, which, despite their highly similar sequences and structures, have been suggested to belong to two different subclasses of PYLs, one being dimeric and relying on binding to ABA to inhibit downstream type 2C protein phosphatases (PP2Cs) and the other being monomeric and able to constitutively inhibit downstream PP2Cs without ABA. MD simulations have been carried out on these proteins in various monomeric or complexation states. Analyses of the simulations unambiguously confirm that ABA has large effects on the conformational dynamics of PYR1 but not PYL10, whereas a downstream PP2C has much larger effects on PYL10 than on PYR1. The differentiated effects are consistent with the functional differences between the two proteins. Potential of mean forces (PMFs) calculated by umbrella sampling showed that binding to ABA strengthens the PYR1-PP2C complex, increasing the PMF change for dissociation from 7.5 to 12.0 kcal mol(-1). On the other hand, the same PMF change for an apo-PYL10-PP2C complex was computed to be 9.5 kcal mol(-1), suggesting stronger binding in apo-PYL10-PP2C than in apo-PYR1-PP2C. Several specific sequence features that may contribute to the functional differentiation between PYR1 and PYL10 are suggested based on the intersubunit residue-residue contacts occurred in the simulations.