Structural Biochemistry/Nucleic Acid/RNA/RNA Secondary Structure

Basis of RNA

 * -RNA bases: A,G,C,U
 * -Base Pairs: A-U, G-C
 * -non-canonical pairs: G-U
 * -Stability: G-C > A-U > G-U
 * -Single Stranded: strand folds upon it to form base pairs; can have a diverse form of secondary structure

Structure Rules

 * 1) Base pairing stabilize the structure
 * 2) Unpaired sections-loops destabilize the structure
 * 3) When a base in one position changes, the base it pairs to must also change to maintain the same structure-covariation

Representations

 * -Most base pairs are non-crossing base pairs: -any two pairs (i, j) and (i’, j’) -> i < i’ <j’ < j or i’ < i < j < j’

Circular Representation

 * -Base pairs of a secondary structure represented by a circle
 * -Arc drawn for each base pairing in the structure

Combinatorics

 * -The number of RNA secondary structures for the sequence: (Recurrence Relation)
 * S(0)=S(1)=S(2)=1
 * S(n+1)=S(n)+ƩS(j-1)S(n-j), (n≥2)
 * -There are approximately 1.3 billion RNA structures of length n is 27

Types of regions

 * 1)	Hairpin Loop - 4 or more bases long for each loop


 * 2)	Bulge Loop - bases on one side cannot form base pairs


 * 3)	Interior Loop - bases on both sides cannot form base pairs


 * 4)	Multi Loop (Junctions) – 2 or more double stranded regions converge to form a closed structure

Structure Prediction Methods

 * 1) Maximize Base Pairs
 * -Determine set of maximal base pairs
 * -Align bases based on ability to pair up to determine the optical structure
 * -Nussinov Algorithm: 4 ways to get the optimal structure between i and j
 * -Find strucuter with the most base pairs: A-U and G-C


 * 2) Minimize Energy
 * -Determine maximum of scores for 4 structures at a particular position
 * -Stacks are the dominant stabilizing force
 * -Energy minimization algorithm predicts the secondary structure by minimizing the free energy
 * -Require estimation of energy terms contributing to secondary structure
 * -Dynamic programming approach:
 * 1)	Initialization
 * 2)	Recursion
 * 3)	Traceback
 * -Does not require prior sequence alighnment
 * -Energy associated with any position is only influenced by local sequence and structure