RNA Folding

1
RNA Folding

• Xinyu Tang
• Bonnie Kirkpatrick

2
Overview

• Introduction to RNA
• Previous Work
• Problem
• Hofackers Paper
• Chen and Dills Paper
• Modeling RNA Folding with PRM

3
Introduction to RNA
4
Composition of Ribonucleic Acid

• A polymer (sequence) of ribonucleoside-phosphates
• Ribose (sugar)
• Phosphoric Acid
• Organic bases
• Adenine (A)
• Guanine (G)
• Cytosine (C)
• Uracil (U)

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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

6
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

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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
  lt j and i, j with i lt j, then
• If i i, then j j
• Each base can appear in only one contact pair
• If i lt j, then i lt i lt j lt j
• No pseudo-knots
• Can be represented as planar graphs

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Representations of RNA

• M Multi-loop
• I Internal-loop
• B Bulge-loop
• H hairpin-loop
• W-C pairs
• - GU pairs

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Representations (cont.)

• Hydrogen bonds between intra-chain pairs are
  represented by circular arcs

All representations are equivalent
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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

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Previous Work
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Maximum Matching Problem

• Watermann and Nussinnov Algorithms
• Finding the conformation with the maximum
  possible number of intra-chain contacts
• Computed using dynamic programming

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Minimum Energy Problem

• Zuker and Stiegler Algorithm
• Predicts the native structure by finding the
  conformation 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
  occurrences in an ensemble of all possible
  structures

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Problem
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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

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Elements of the Problem

• Model
• Sampling Pattern
• Node Connection Methods
• Analysis Techniques

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Hofackers Paper
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Chen and Dills Paper
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Modeling RNA Folding with PRM
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Secodary vs Tertiary Structure

• Tertiary structure can only be determined for
  tRNA
• Secondary structure predictions only approximate
  tertiary structure
• For each set of intra-chain contacts, there is an
  ensemble of possible tertiary structures
• Chen and Dill were able to use a