predicting coaxial stacking by free energy minimization
Download
Skip this Video
Download Presentation
Predicting Coaxial Stacking by Free Energy Minimization

Loading in 2 Seconds...

play fullscreen
1 / 29

Predicting Coaxial Stacking by Free Energy Minimization - PowerPoint PPT Presentation


  • 94 Views
  • Uploaded on

Predicting Coaxial Stacking by Free Energy Minimization. David Mathews Department of Biochemistry & Biophysics University of Rochester Medical Center. Predicting Coaxial Stacking:. Rahul Tyagi. Multibranch Loops (MBL). http://www.stanford.edu/~esorin.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Predicting Coaxial Stacking by Free Energy Minimization' - sumi


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
predicting coaxial stacking by free energy minimization

Predicting Coaxial Stacking by Free Energy Minimization

David Mathews

Department of Biochemistry & Biophysics

University of Rochester Medical Center

multibranch loops mbl
Multibranch Loops (MBL)

http://www.stanford.edu/~esorin

a step towards tertiary structure prediction
A step towards tertiary structure prediction

1 stacked on 2 mediated by mismatch

Secondary structure representation

2 flush stacked on 3

flush and mismatch mediated stacking
Flush and Mismatch-Mediated Stacking

Mismatch-mediated stacking

Flush stacking

  • Stacking stabilization: Thought to arise from hydrophobic effect, charge
  • interactions and van der Waals interactions.
predicting coaxial stacking1
Predicting Coaxial Stacking
  • Find all the non-redundant RNA crystal structures from NDb.

Hypothesis

“The stacking configuration with lowest free energy as predicted by

Nearest Neighbour Parameters exists in naturally occurring RNAs.”

  • Predict the coaxial stacking configuration by finding free energy of all possible configurations in all MBLs.
  • Compare predictions with crystal structures.
secondary structure to predicted stacks
Secondary structure to predicted stacks

http://www.rna.icmb.utexas.edu/

nearest neighbor model for coaxial stacking
Nearest Neighbor Model for Coaxial Stacking

Model based on work by Walter, Kim and others in Turner lab.

atom coordinates to identified stacks
Atom Coordinates to Identified Stacks

http://rna.ucsc.edu/rnacenter/ribosome_images.html

stacking definition for verification
Stacking Definition for Verification

Basepair center and basepair plane definition

from Biochemistry 2nd Ed. by Garrett & Grisham

coaxial stacking discovery
Coaxial Stacking Discovery

N1

Criteria for stacking

a. Basepair plane tilt

< 26º for Flush / 32º for MM

N2

N1

b. Distance between basepair “centers”

< 5 Å for Flush / 12 Å for MM

(based on Gabb et al., J. Mol. Graph., 14, 6-11

Burkard et al., JMB, 290, 967-982

and Gendron at al., JMB, 308, 919-936

D1-2

stacking definition for verification1
Stacking Definition for Verification

c. Basepair shear

angle between inter-center vector

and baseplane normal vectors

< 60º

capturing complex stacks
Capturing Complex Stacks

relaxed tilt and distance criteria:

distance of basepair centers from normal to the other basepair < 10 Å

capturing complex stacks1
Capturing Complex Stacks

Base Stack Cascade

rna structure dataset
RNA structure dataset

The ribosome RNA structures provide maximum data.

suboptimal configurations the problem with lowest free energy
Suboptimal ConfigurationsThe Problem with Lowest Free Energy

Just 4 out of 51 possible configurations!

Consider,

K3/2 < K1, K2 < K3

A stack is more probable if it is part of many different configurations of low free energy.

partition function and configuration probabilities
Partition Function and Configuration Probabilities
  • PT = Σi exp(-ΔGi/RT) where i varies over ALL the possible configurations.
  • PR,S = Σj exp(-ΔGj/RT) where j varies over all the possible configurations that have stack S.
  • ps = PR,S / PT
probability threshold for prediction
Probability Threshold for Prediction

Both plots show a sharp drop at 0.70

So 70% was chosen to be the cut-off value for prediction

conclusion
Conclusion:
  • Predicting coaxial stacking by free energy minimization provides a method to predict the topology of tertiary structure.
ad