TERTIARY STRUCTURE PREDICTION- COMPARATIVE MODELLING- MODELLER, RASMOL from bioinformatics

1. TERTIARY STRUCTURE PREDICTION
COMPARATIVE MODELLING- MODELLER, RASMOL
Presented by,
Kaveri

2. WHAT IS A TERTIARY STRUCTURE OF PROTEIN?
• Tertiary Structure is the folding of the total chain
• Secondary structure linked by turns and loops.
• Stability - non-bonding interactions & the disulfide bond.
Tertiary structure

3. WHAT IS TERTIARY STRUCTURE PREDICTION?
• Inference of the three-dimensional structure of a protein
from its amino acid sequence.
• Prediction of its folding and its secondary and tertiary
structure from its primary structure.
• Sites for calculating and displaying the 3-D structure of
oligosaccharides and proteins.
• Eg: ab initio, Homology modelling, protein threading etc

4. COMPARATIVE MODELLING
• Predicts 3 dimensional structure of a given protein sequence
(target) based on an alignment to one or more known protein
structures (templates).
• Uses experimentally determined protein structures as templates
to predict the conformation of another protein that exhibits
amino acid sequence homology.

5. • If similarity between the target sequence and the template sequence is detected, structural
similarity can be assumed.
• A similar structure can be predicted if sequence similarity is about or above 35%.

6. • The similarity of structures is very high in the so-called "core regions“.
• core regions - comprised of secondary structure elements such as a-helices and b-sheets.

7. STEPS FOR COMPARATIVE MODELING
1. Find one or more proteins in the PDB that
exhibit sequence similarity to your protein
2. Construct a sequence alignment
3. Decide which regions are structurally
conserved (SCR): helices, strands
4. Construct loops either by analogy or from a
database
5.Place side-chains: use existing
conformational info and rotamer databases.
6. Refine the model: packing, surface
accessibilities, energy calculations
7. Validate the model
8. Iterate all of the above steps to remove
errors

8. MERITS AND DEMERITS
MERITS
• Enrichment of graphical methods
• Formulation to incorporate domain knowledge
• Effective for protein structure prediction
• Solution for long range interaction
DEMERITS
• Manual feature extraction
• Difficulty in verification
• High complexity

9. MODELLER
• Program for Comparative protein structure modelling by satisfaction of spatial restrains.
• Used for comparative modeling of protein three-dimensional structures.
• The user provides an alignment of a sequence to be modeled with known related structures
MODELLER automatically calculates a model containing all non-hydrogen atoms.
• Implements comparative protein structure modeling by satisfaction of spatial restraints.

10. • Additional tasks
• de novo modeling of loops in protein structures
• Optimization of various models of protein structure with respect to a flexibly defined
objective function
• Multiple alignment of protein sequences and/or structures
• Clustering
• Searching of sequence databases
• Comparison of protein structures etc.

11. • MODELLER is written in Fortran-90 and is meant
to run on a UNIX system.
• Available free of charge to academic non-profit
institutions.
• https://salilab.org/modeller/ - website.

12. RASMOL
• It is a molecular graphics bio-software used for the visualization of proteins, nucleic acids,
and small molecules.
• This molecular viewer is aimed at display, teaching and generation of publication quality
images.
• It allows user to display the molecule in a variety of structural representation.
• Ras Mol can be downloaded from http://www.umass.edu/microbio/rasmol.

13. FEATURES
• Ras Mol displays all or any part(s) of a molecule or
molecular complex.
• It can rotate the displayed image
• Different parts of the structure can be coloured to convey
structural information, and can be labeled
• It can report information about atoms including name of the
atom, bond distances, angle etc.
• It can represent structures in different models (ball and stick
models, ribbons, strands, cartoons etc.).

14. HOW TO USE RAS MOL ? 2 windows
Graphics
window
command
Line window
Graphics window
• The top of the graphics window has a menu bar of pull-
down menus such as File, Display, Colours, Export,
Options, and Help.
• The molecules appears in initially as a wire –frame
structure with a black back- ground.
• With the help of the Display and Colours menus, we can
change the display from wire-frame to back bone, sticks,
space fill, or various ribbons, and we can also change the
colour of the molecule.

15. Command Line window
• It is used for selection of those portions of the molecules of
interest.
• The commands offer the possibility for changing the colour.
• H-bonding involved in the secondary structure of the protein
can be displayed.
• Showing the ligands or coenzymes in space filling mode, all
are colour coded to make the various features easily
identifiable.

16. USES
• It is a software to view, handle, and
analyze macromolecular 3D structures.
• It determines overall shape and size of a
molecule.
• To locate or predict possible binding
sites of a ligand.
• To study evolutionary process at
molecular level.

17. THANK YOU