Peptide nucleic acid (PNA) is a neutral nucleic acid analogue that base pairs with itself and natural nucleic acids. PNA-nucleic acid complexes are more thermally stable than the corresponding complexes of natural nucleic acids. In addition, PNA is biostable and thus used in many antisense and antigene applications to block functional RNA or DNA via sequence-specific interactions. We have recently developed force field parameters for molecular dynamics (MD) simulations of PNA and PNA-involving duplexes with natural nucleic acids. In this work, we provide the first application of this force field to biologically relevant PNA sequences and their complexes with RNA. We investigated thermal stabilities of short PNA-PNA, PNA-RNA, and RNA-RNA duplexes using UV-monitored thermal denaturation experiments and MD simulations at ambient and elevated temperatures. The simulations show a two-state melting transition and reproduce the thermal stability from melting experiments, with PNA-PNA being the most and RNA-RNA the least stable. The PNA-PNA duplex also displays the highest activation energy for melting. The atomistic details of unfolding of PNA duplexes suggest that all PNA-PNA bases melt concomitantly, whereas the RNA-RNA and PNA-RNA are destabilized from the termini toward the central part of the duplexes.