This document discusses protein tertiary structure prediction and comparative modeling. It defines tertiary structure as the folding of the total protein chain linked by secondary structure elements. Comparative modeling predicts a protein's 3D structure by aligning its sequence to known protein templates that have over 35% sequence similarity, especially in core regions like helices and sheets. The document outlines the steps of comparative modeling and describes software like MODELLER for modeling and RASMOL for visualization.

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