![[DNA_orbit_animated.gif|150]]
# Nucleic Acids
https://library.med.utah.edu/NetBiochem/pupyr/pp.htm
**Nucleic acids** are one of the four main classes of [[Biological Macromolecules]].
The two primary forms of nucleic acids are *deoxyribonucleic Acid (DNA)* and *Ribonucleic Acid (RNA)*.
- Primary purpose is information storage (Genetics, Hereditary, Reproduction)
- Have complementary pairs
- Guanine & Cytosine (3 Hydrogen Bonds)
- Adenine & Thymine (2 Hydrogen Bonds)
> [!info] Biotechnology Applications
> G-C base pairs **require more energy** to break than A-T pairs due to the *additional hydrogen bond present*.
>
> This often impacts lab techniques such as [[Polymerase Chain Reaction (PCR)|PCR]] which requires a specific temperature to be calculated based on the amount of each base present.
## Structure of Nucleic Acids
### Primary Chemical Structure
**Nucleotides** (within both DNA and RNA) are composed of:
1. A nitrogenous base
2. A five-carbon sugar
3. A phosphate group
Nucleosides lack the phosphate group
![[Pasted image 20240225035850.png]]
![[Pasted image 20240429163423.png]]
#### Nitrogen Bases
> [!NOTE] Purines vs Pyrimidines
>
> **Pyrimidines** *(Single-Ringed Structures)*:
> - Cytosine
> - Thymine
> - Uracil
>
> **Purines** *(Double-Ringed Structures)*:
> - Guanine
> - Adenine
>
##### Base Pairings
The two canonical base pairings
##### Non-Canonical Bases & Pairings
Non-canonical base pairs
- In Hoogsteen base pairs, purines rotate and form non-canonical H-bonds with its cognate base, leading to the formation of new potential H-bonds at the unused positions
- (syn adenine base with anti thymine base)
#### Five-Carbon Sugar
The orientation of these five-carbon sugars are important in the process of transcription and translation (5' -> 3' vs 3' -> 5').
The opposite strand of DNA is orientated in the opposite direction, making them **anti-parallel** to eachother.
The five different carbons within the sugar are named in clockwise order to track the orientation.
### Secondary Structure
> See also:
> - [[Nucleic Acid Structure Prediction]]
![[Pasted image 20250508073123.png|281]]
**Conventional Structures:**
| Structure | Description |
| ------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| **Hairpin Loops** | A structure with two ends of a single-stranded region (loop) connecting a base-paired region (stem). |
| **Bulge Loops** (pimples) | A single stranded region connecting two adjacent base-paired segments so that it “bubbles” out in the middle of a double helix on one side. |
| **Interior Loops** | Refers to two single-stranded regions on opposite strands connecting two adjacent base-paired segments. It can be said to “bubble” out on both sides in the middle of a double helical segment. |
| **Multibranch Loops** | Refers to a loop that brings three or more base-paired segments in close vicinity formint a multifurcated (branching) structure.<br><br>Also called helical junctions. |
| *Pseudoknot Loop* | Refers to the base pairing formed between loop residues within a hairpin loop and residues outside the hairpin loop. |
| *Kissing Hairpin* | Refers to hydrogen bonded interactions formed between the loop residues of two hairpin structures. |
| *Hairpin-Bulge Contact* | Refers to the interactions between loop residues of a hairpin loop and a bulge loop |
![[Pasted image 20250508080151.png|300]]
The last three motifs are known as *supersecondary structures*.
#### Stabilization of Nucleic Acids
“not all DNA sequences were made equally”
- the stability of a nucleic acid chain can vary depending on the sequences
There are three major factors influencing the stability of double-stranded nucleic acids
1. Base Pairing
2. Stacking Interactions
3. Ionic Interactions
While hydrogen bonding is essential for complimentary base pairing, it is important to remember that in the grand scheme they contribute little to the stability of nucleic acid structure
The phosphate backbone surrounding the outside of dsDNA contains a partial negative charge, leading to the formation of a hydration shell with water molecules
#### Stacking Interactions
> See also:
> - [[Intermolecular Forces]]
https://www.chem.ucla.edu/~harding/IGOC/A/aromatic_aromatic_interaction.html
#### Shielding of Negative Phosphate Backbone
The phosphates within the backbone of DNA and RNA contains a negative charge which significantly affects the overall charge of the strand.
To mitigate any repulsion between these negative charges and to stabilize the double helical structure, metal ions, such as magnesium ions ($Mg^{2+}$), are often associated with the phosphate backbone.
## Deoxyribonucleic Acid (DNA) vs Ribonucleic Acid (RNA)
RNA is less stable than DNA due to its chemical structure:
- RNA is more susceptible to degradation due to the 2' hydroxyl group (nucleophilic) adjacent to the phosphodiester linkages in RNA
- mRNA 5' cap, polyA tail can hold off degradation for a short time
- DNases require metal ions for activity and can be inactivated with chelating agents (EDTA), but RNases do not use metal ions.
![[Nucleic Acids.png]]
## Additional Structures
- DNA
- RNA
- nucleotides
- nucleoside
- nucleosides
### Functional RNA
Functional strands of RNA can form **ribozymes** which are found within the structure of the ribosome organelles within eukaryotic cells