Locked nucleic acid (LNA) is a chemical modification which introduces a −O–CH2– linkage in the furanose sugar of nucleic acids and blocks its conformation in a particular state. Two types of modifications, namely, 2′-O,4′-C-methylene-β-d-ribofuranose (β-d-LNA) and 2′-O,4′-C-methylene-α-l-ribofuranose (α-l-LNA), have been shown to yield RNA and DNA duplex-like structures, respectively. LNA modifications lead to increased melting temperatures of DNA and RNA duplexes, and have been suggested as potential therapeutic agents in antisense therapy. In this study, molecular dynamics (MD) simulations were performed on fully modified LNA duplexes and pure DNA and RNA duplexes sharing a similar sequence to investigate their structure, stabilities, and solvation properties. Both LNA duplexes undergo unwinding of the helical structure compared to the pure DNA and RNA duplexes. Though the α-LNA substituent has been proposed to mimic deoxyribose sugar in its conformational properties, the fully modified duplex was found to exhibit unique structural and dynamic properties with respect to the other three nucleic acid structures.