RNA Folding Xinyu Tang Bonnie Kirkpatrick. Overview Introduction to RNA Previous Work Problem...
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Transcript of RNA Folding Xinyu Tang Bonnie Kirkpatrick. Overview Introduction to RNA Previous Work Problem...
Overview
Introduction to RNA Previous Work Problem Hofacker’s Paper Chen and Dill’s Paper Modeling RNA Folding with PRM
Composition of Ribonucleic Acid
A polymer (sequence) of ribonucleoside-phosphates
Ribose (sugar) Phosphoric Acid Organic bases
– Adenine (A)– Guanine (G)– Cytosine (C)– Uracil (U)
Complementary Base Pairs
Canonical base pairs– Watson-Crick base pairs
C-G A-U Stable base pairs Hydrogen bonds
– Weaker G-U wobble pair
Non-canonical base pairs– Some of them stable
RNA Tertiary Structure
A complex folding in 3-dimensions (similar to protein tertiary structure)
A specific folding is referred to as a conformation
Pseudo knots are considered a tertiary structure, rather than a secondary structure
RNA Secondary Structure
A secondary structure conformation is specified by a set of intra-chain contacts (base pairs) that follow certain rules
Given any two intra-chain contacts [i, j] with i < j and [i’, j’] with i’ < j’, then:1) If i = i’, then j = j’
• Each base can appear in only one contact pair
2) If i’ < j, then i < i’ < j’ < j• No pseudo-knots
Can be represented as planar graphs:
Representations of RNA
M: Multi-loop I: Internal-loop B: Bulge-loop H: hairpin-loop •: W-C pairs -: GU pairs
Representations (cont.)
Hydrogen bonds between intra-chain pairs are represented by circular arcs
All representations are equivalent
Representations (cont.)
Contact Map
A dot is placed in the ith
row and jth column of a triangular array to represent the intra-chain contact [i, j]
Maximum Matching Problem
Watermann and Nussinnov Algorithms– Finding the conformation with the maximum possibl
e number of intra-chain contacts– Computed using dynamic programming
Minimum Energy Problem
Zuker and Stiegler Algorithm– Predicts the native structure by finding the conformati
on with the minimum energy
Modified Zuker Algorithm– Generates a set of conformations that lie within some
energy range of the predicted native conformation
McCaskill Algorithm– Calculates the frequency of intra-chain contact occurr
ences in an ensemble of all possible structures
Energy Landscapes
Native conformations of RNA can be predicted with accuracy
But the not much is known about the kinetics and thermodynamics of the folding
Energy landscapes show us what different conformations the RNA goes through as it folds