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Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

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Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
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Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
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The proto-Nucleic Acid Builder: a software tool for constructing nucleic acid analogs.

Asem Alenaizan1,2, Joshua L Barnett3, Nicholas V Hud1

  • 1School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.

Nucleic Acids Research
|December 10, 2020
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Scientists developed proto-Nucleic Acid Builder, an open-source program for modeling Xeno Nucleic Acids (XNAs). This tool aids in designing novel nucleic acid analogs and exploring potential pre-RNA molecules.

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Area of Science:

  • Biochemistry
  • Computational Biology
  • Synthetic Biology

Background:

  • DNA and RNA helical structures are known, guiding early polymer modeling.
  • Xeno Nucleic Acids (XNAs) offer diverse structural and chemical properties due to alternative backbones.
  • The vast chemical space of XNAs necessitates computational approaches for exploration.

Purpose of the Study:

  • To introduce the proto-Nucleic Acid Builder (pNAB) software.
  • To facilitate the design of novel XNA polymers with alternative backbones and nucleobases.
  • To aid in the search for potential pre-RNA molecules in early life evolution.

Main Methods:

  • Development of an open-source program, proto-Nucleic Acid Builder (pNAB).
  • Implementation of a torsion-driven conformation search procedure for nucleic acid analog modeling.
  • Validation of the program's accuracy against experimental structures of DNA and RNA.

Main Results:

  • The pNAB program accurately predicts nucleic acid analog structures.
  • The modeling correctly demonstrates the link between helical structure and backbone conformation in DNA and RNA.
  • The software accelerates the search for plausible nucleic acid analogs and guides their rational design.

Conclusions:

  • The proto-Nucleic Acid Builder is a valuable tool for XNA development and pre-RNA research.
  • Computational modeling significantly aids in exploring and designing novel nucleic acid structures.
  • Understanding XNA structures provides insights into the fundamental properties of genetic polymers.