Scribd
Upload
27 views30 pages

Lecture 12 (Structural Bioinformatics) Cbdb30310921cec2c447276bb2d88a8f

Structural bioinformatics focuses on the representation, storage, retrieval, analysis, and display of structural information at atomic and sub-cellular scales, emphasizing the relationship between protein structure and function. Techniques such as X-ray crystallography and NMR are used to determine protein structures, while computational methods like homology modeling facilitate structure prediction from amino acid sequences. The Protein Data Bank (PDB) serves as a key resource for accessing three-dimensional structures of proteins and biological macromolecules, aiding in drug design and understanding protein interactions.

Uploaded by

اشرف ادم
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
27 views30 pages

Lecture 12 (Structural Bioinformatics) Cbdb30310921cec2c447276bb2d88a8f

Structural bioinformatics focuses on the representation, storage, retrieval, analysis, and display of structural information at atomic and sub-cellular scales, emphasizing the relationship between protein structure and function. Techniques such as X-ray crystallography and NMR are used to determine protein structures, while computational methods like homology modeling facilitate structure prediction from amino acid sequences. The Protein Data Bank (PDB) serves as a key resource for accessing three-dimensional structures of proteins and biological macromolecules, aiding in drug design and understanding protein interactions.

Uploaded by

اشرف ادم
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 30

BIOINFORMATICS

Introduction to Structural
bioinformatics
Lecture #12
Anas Abdelrahman Elzein
PhD Biochemistry and Molecular Biology
Zhejiang University
1
February 2025
Structural bioinformatics
Structural bioinformatics is the
sub-discipline of bioinformatics
that focuses on the
representation, storage retrieval,
analysis, and display of structural
information at the atomic and sub-
cellular scales.
2
STRUCTURE → FUNCTION relationship

Determining structure is often critical in


understanding what a protein does (Function)

Tow main techniques to determine the


structure:-

• X-ray crystallography
• NMR (Nuclear Magnetic Resonance)
3
X-ray Crystallography & NMR
➢ Obtained much more slowly.
➢ Techniques involve elaborate technical procedures
➢ Many proteins fail to crystallize at all and/or
cannot be obtained or dissolved in large enough
quantities for NMR measurements
➢ The size of the protein is also a limiting factor for
NMR

With a better computational


method this can be done
extremely fast.
4
Proteins
• Proteins play a crucial role in all biological
processes with a broad range of functions.
• The activity of an enzyme or the function of a
protein is governed by the three-dimensional
structure.
• Shape depends on particular Amino Acid
Sequence.
• Shape gives SPECIFIC function

5
Four Levels of Protein Structure
Proteins have four levels of structure: primary,
secondary, tertiary, and quaternary.

Primary structure refers to the amino acid


sequence of a protein.
Secondary structure refers to the conformation
of the polypeptide backbone. Examples of
secondary structures are helices (α-helix), and
pleated sheets (β-pleated sheet
6
Tertiary structure of a protein refers to its three-
dimensional structure—that is, further folding
of the secondary structure in the three-
dimensional space.

Quaternary structure refers to a structure


achieved by proteins composed of more than
one polypeptide chain. Each polypeptide chain,
called a subunit, has its own primary, secondary,
and tertiary structure.

7
8
Can we predict structure from
sequence?
GCTCCTCACTGTCTGTGTTTATTCTTTTAGCTTCTTC
AGATCTTTTAGTCTGAGGAAGCCTGGCATGTGCA
AATGAAGTTAACCTAA

9
Structure Prediction

?
GPSRYIVMVVM…

Note:-
Secondary structure prediction is hard,
tertiary structure prediction is even harder. 15
Structure Prediction
It could be determined in silico using
comparative or homology modelling, which
allows the construction of a 3D model of the
"target" protein from:-

• Its amino acid sequence, and


• An experimental 3D structure of a related
homologous protein (the "template").
11
Secondary structure prediction
Tools
• Jpred
(http://www.compbio.dundee.ac.uk/www-jpred/)
• PHD
(https://npsa-prabi.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_phd.html)

• PredictProtein
(https://www.predictprotein.org/)
• …..etc

12
13
PDB
https://www.rcsb.org/

The Protein Data Bank (PDB) is a web accessible


database that contains information about the
three-dimensional structures of large biological
molecules.
Protein Data Bank Contains all publicly available
experimentally determined structural models of
proteins and nucleic acids (determined by x-ray
crystallography and NMR)

14
PDB
Since structure and function are closely related,
the PDB aims at bridging the gap between the
function of large biomolecules and the role that
they universally play in number of organisms
including bacteria, yeast, plants, mice, and in
healthy as well as diseased humans.
The key to understanding the function of a
molecule is its shape.
VIEWING THE 3D STRUCTURE OF
PROTEINS (AND OTHER BIOLOGICAL
MACROMOLECULES)

The 3D structures of many proteins and


other biological macromolecules have
been determined using various techniques
of modern structural biology. These
structures are deposited in the PDB
database and are given a PDB ID.

16
The PDB ID is a four-character unique
identifier, consisting of numbers and
letters, assigned to a protein or other
biological macromolecule submitted to the
PDB. The PDB is an archive of the structure
of proteins and other biological
macromolecules.

17
• PDB IDs are usually written in uppercase.
Some examples of PDB IDs are 2HHD
(human hemoglobin, deoxy form), 9INS
(pig insulin), and 2VRY (mouse
neuroglobin).

• The PDB can be searched by simply typing


the description, or partial sequence, or
the PDB ID (if known).
18
19
Recall Protein
Sequence
from UniProt

25
Paste and Click Go

26
22
Three-dimensional structure
➢ Helps in the rational design of site-directed
mutations

➢ Can be of great importance for the design


of drugs

➢ Greatly enhances our understanding of


how proteins function and how they
interact with each other, for example,
explain antigenic behaviour, ..... etc
23
Computational methods for Protein
Structure Prediction

John C. Kendrew
Today
and his model of
myoglobin

Max F. Perutz
and his first
high resolution
model of
haemoglobin
29
Homology Modeling
• Simplest, reliable approach
• Basis: proteins with similar sequences tend to
fold into similar structures
• Has been observed that even proteins with
25% sequence identity fold into similar
structures
• Does not work for remote homologs (< 25%
pairwise identity)
The homology modelling procedure:
• Template selection; Select those
structures that will be used as templates.
This step could be done by the modelling
software.

• Target-template alignment; usually using


multiple sequence alignments to map
residues in the query sequence to residues
in the template sequence.
• Model construction; using the sequence
alignment and template structure.

• Model assessment; to assess the quality


of the structure. There is a clear correlation
between the degree of sequence identity
between the target and the model and the
accuracy of the final model

32
• Successful homology modelling depends on
the following:
▪ Template quality
▪ Alignment (add biological information)
▪ Modelling program/procedure (use more than one)

• Always validate your final model!

ProQ Protein Quality Predictor is a network


based predictor that based on a number of
structural features to predicts the quality of a
protein model. http://www.sbc.su.se/~bjorn/ProQ/ 33
Many online homology modelling tools
are available such as:
• SWISS-Model
• Modeller
• I-TASSER
• ……. etc

29
30

You might also like