The proto-Nucleic Acid Builder: a software tool for constructing nucleic acid analogs

Abstract

The helical structures of DNA and RNA were originally revealed by experimental data. Likewise, the development of programs for modeling these natural polymers was guided by known structures. These nucleic acid polymers represent only two members of a potentially vast class of polymers with similar structural features, but that differ from DNA and RNA in the backbone or nucleobases. Xeno nucleic acids (XNAs) incorporate alternative backbones that affect the conformational, chemical, and thermodynamic properties of XNAs. Given the vast chemical space of possible XNAs, computational modeling of alternative nucleic acids can accelerate the search for plausible nucleic acid analogs and guide their rational design. Additionally, a tool for the modeling of nucleic acids could help reveal what nucleic acid polymers may have existed before RNA in the early evolution of life. To aid the development of novel XNA polymers and the search for possible pre-RNA candidates, this article presents the proto-Nucleic Acid Builder (https://github.com/GT-NucleicAcids/pnab), an open-source program for modeling nucleic acid analogs with alternative backbones and nucleobases. The torsion-driven conformation search procedure implemented here predicts structures with good accuracy compared to experimental structures, and correctly demonstrates the correlation between the helical structure and the backbone conformation in DNA and RNA.

Molecular Simulations Matching Denaturation Experiments for N6-Methyladenosine

“…Starting structures for MD simulations were built using the proto-Nucleic Acid Builder . Single strands were generated by deleting one of the chains from duplex structures.…”

Helicene Structure between DNA and Cyanuric Acid: The Role of Noncovalent Interactions

“…All quantum mechanical calculations were performed using the P si 4 package (version 1.4) . The geometries of the base pairs and base steps were prepared using a development version of the proto-Nucleic Acid Builder package and a custom script.…”

Structural Analysis of the Poly(thymidine)–Melamine Assembly

“…The poly(T) backbones were optimized using the torsion-driven approach of the proto-Nucleic Acid Builder package (version 1.5). 32 In addition to these five 15-mer initial structures, the experimentally reported hexamer structure (PDB ID: 6WK7) 23 was also used. The initial systems were solvated in a water box with 16 Å padding distance and neutralizing sodium ions using the AmberTools package (version 21).…”

“…Poly­(T) oligomers (either 3′ → 5′ or 5′ → 3′ strands) were constructed such that the nucleobases have an appropriate, planar hydrogen bonding geometry with the MEL monomers. The poly­(T) backbones were optimized using the torsion-driven approach of the proto-Nucleic Acid Builder package (version 1.5) . In addition to these five 15-mer initial structures, the experimentally reported hexamer structure (PDB ID: 6WK7) was also used.…”