Nanoscale structures and mechanics of peptide nucleic acids

Peptide nucleic acids (PNAs) are charge-neutral polyamide oligomers having extremely favorable thermal stability and high affinity to cell membranes when coupled with cationic cell-penetrating peptides (CPPs), as well as the encouraging antisense and antigene activity in cell-free systems. The study of the mechanical properties of short PNA molecules is rare both in experiments and theoretical calculations. Here, we studied the microscopic structures and elastic properties; namely, persistence length, stretch modulus, twist-stretch coupling, and structural crookedness of double-stranded PNA (dsPNA) and their hybrid derivatives using all-atom MD simulation and compared them with those of double-stranded DNA (dsDNA) and double-stranded RNA (dsRNA). The stretch modulus of the dsPNA is found to be ∼160 pN, an order of magnitude lower than that of dsDNA and smaller than dsRNA, respectively. Similarly, the persistence length of dsPNA is found to be ∼35 nm, significantly smaller than those of dsDNA and dsRNA. The PNA-DNA and PNA-RNA hybrid duplexes have elastic properties lying between that of dsPNA and dsDNA/dsRNA. We argue that the neutral backbones of the PNA make it less stiff than dsDNA and dsRNA molecules. Measurement of structural crookedness and principal component analysis additionally support the bending flexibility of dsPNA. Detailed analysis of the helical-rise coupled to helical-twist indicates that the PNA-DNA hybrid over-winds like dsDNA, while PNA-PNA and PNA-RNA unwind like dsRNA upon stretching. Because of the highly flexible nature of PNA, it can bind other biomolecules by adopting a wide range of conformations and is believed to be crucial for future nanobiotechnology research studies.