The document provides a comprehensive overview of protein structure and analysis, highlighting the significance of amino acids, the formation of peptide bonds, and the relationship between protein structure and function. It outlines the different levels of protein structure, including primary, secondary, tertiary, and quaternary, as well as the techniques for determining 3D structures, such as X-ray crystallography and NMR studies. Additionally, it discusses protein modeling techniques, including homology and threading modeling, emphasizing their importance in understanding protein functions and designing drugs.

1. Protein structure analysis
Prepared by:
Anfal Izaldeen ALKATEEB

2. Protein structure
• Proteins : is made of chain of amino acids ( amino acid= monomers) therefor
the protein is polymers .
• The proteins are made up of carbon, hydrogen, oxygen and nitrogen.
• Amino acid :
Amino acid — amino acid
Peptide bond with removal of
water

3. Protein analysis protein shape determines
function.
1. Amino acid order determines the shape( conformation) of protein.
2. Conformation determines function.
3. Function depends on its ability to recognize and bind a molecule.
Many of amino acids jointed by peptide bond formed polypeptide
chain which is not brunched.
(amino acid in poly peptide is called residue.)

4. The protein divided into
groups
1. Globular protein: these are molecules there are often spherical in shape
have a chemical function ex: enzyme .
2. Fibrous protein: these have structural role. They give strength or
elasticity to a particular tissue ex: collagen and keratin in hair.

5. Protein structure
• Proteins are long sequences formed out of 20 different amino acid
residues that in physiological conditions adopt a unique 3-D
structure. Knowledge of the protein structure allows the
investigation of biological processes more directly ,with higher
resolution and finer detail.
• Bio chemists have distinguished several levels of structure
organization of proteins.
•
•

6. Proteins levels
• Primary structure : a sequence of amino acid in a polypeptides
chain.
• Secondary structure : refers to highly regular local sub
strictures. These sec. str. Are defined by patterns of hydrogen
bonds between the main- chain peptide groups. Both of α helix
and β sheets represent away of saturating all the hydrogen
bond donors and accepted in the peptide backbone.
• Bonds a helix is the most common secondary
Structure .

7. Tertiary protein structure
• Tertiary structure is the 3D conformation of polypeptides.
• The α helixes and β- pleated- sheets are folded into a compact globular
structure. This structure elements when arrangement in space , creating
structural Motifs and folds ( tertiary structure ).
• The knowledge of the 3D structure of polypeptides gives researchers very
important information to infer the function of the protein in the cell
• structural functions ;catalysis in chemical reactions;
• transport and storage; regulatory functions;
• gene transcription control and recognition
• functions

8. 3D protein structure analysis
• The shape is maintain by hydrogen bonds and the strong bonds disulfide bridge
which form between the sulphur containing amino acid molecule.
• The difficulty in determining and finding out the 3-D structure of proteins has
generated a large discrepancy between the volume of data (sequences of amino
acid residues) generated by the Genome Projects and the number of 3-D
structures of proteins which are currently known.
• Only a tiny portion of protein sequences have experimentally solved three-
dimensional structures.
• The function of protein is depend on its tertiary structure if
this distributed, its losses its activity.

9. 3D protein structure
• the folding which formed by α helix and β sheets is driven by the nonspecific
hydrophobic interactions( the burial of hydrophobic residues from water), but
the structure is stable only when the parts of protein domains are locked into
a place by specific tertiary interaction such as salt bridges ,hydrogen bonds
and tight packing of side chains and disulfide bond. the disulfide bonds are
extremely rare in cytosolic protein, since the cytosolic is generally a reducing
environment.

10. Domain
• An independent unit of the 3D protein structure is called
domain.
• Polypeptide chain containing more than 200 residues
usually fold into two or more globular clusters( this
cluster is domain).
• Fundamental functional and 3D structure of proteins
• Domains often have a specific function such as the
binding of small molecules. Many domains are
structurally independent units that have the
characteristic of small globular protein.
• A protein domains is assigned a certain type of fold
• Domains with the same fold may or may not be related
to each other functionally .

11. 3D protein structure analysis
Determination of tertiary structure
• The known protein structure have come to light
through:
• X rays crystallographic studies.
• Nuclear magnetic resonance studies.
• The atomic coordinates of most of these structures
are deposited in a database known as the Protein
Data Bank (PDB).
• It allows the tertiary structures of variety of proteins
to be analyzed and compared .
• The PDB have been classified into more than 1000
different unique folds.

12. Quaternary structure
• The protein consists more than one polypeptides.
• The different of polypeptide chains bind to gather to form a whole molecule.
• The biological function of some molecules is determined by multiple
polypeptide. . arrangement of polypeptide sub unite is quaternary by non covalent
• Ex: insulin is made up of two chains while hemoglobin is made up of four
chains.

13. 3 D structure analysis
Interaction Stabilizing 3 D Structure
The final shape is determined by a variety of bonding interactions between the
side chains on the amino acids. The interactions occur between R group & R
group and backbone.
Hydrogen bonds, Ionic bonds , Disulphide bridges
hydrophobic interaction ( often in interior of protein).
Covalent bonds : disulfide bridge formed between the sulfhydryl group
(SH) of cystein amino acid.

14. 3 D modeling of protein
• Protein modeling : provide a solid bases for:
1. Structure based drug design
2. rational design of proteins with increased stability or novel function
3. They can be used to examine sequence-structure-function
relationships, interactions, active sites, and more.
• Three dimensional structures provide a wealth of information on the
biological function and the evolutionary history of macromolecules.
• Successful model building requires at least one experimentally solved
3D structure (template) that has a significant amino acid sequence
similarity to the target sequence. Various structural genomics
initiatives were started in the last few years, aiming to speed up the
elucidation of new protein structures.
•

15. Proteins modeling
Homology protein
• Portion of 2 proteins with
similar amino acids :
*conserved region.
* highly similar proteins
may have same basic
function
Homology modeling
• Comparative modeling of
protein
• To predict protein structure
based on known 3D shape
protein as a templet.

16. Homology modeling
• The structure of protein is determined by its amino acid sequence and Structure is much
more conserved than sequence during evolution.
Homology modeling based on two major observation

17. What is the homology modeling
• Predicts the 3D structure of a
given protein sequence
(target) based on an
alignment to one or more
known protein
structure(templates).
• if similarity between the target
sequence and the template
sequence is detected,
structural similarity can be
assumed.
• in general 30% sequence
identity is required to
generate an useful model

19. 2. A b initio modeling
• A b initio modeling conducts a
conformational search under
the guidance of a designed
energy function.
• This procedure usually
generates a number of possible
conformation (structure
decoys). and final models are
selected from them.

20. a successful AB initio modeling depends
on 3 factors:
• 1. a accurate energy function with which the native
structure of protein corresponds to the most
thermodynamically stable state, compared to all possible
decoy structures.
• 2. an efficient search method which can quickly identify the
two- energy states through conformation search.
• 3. selection of native- like model from a pool of decoy
structure.

21. 3. Threading modeling of protein
• Protein threading , also known as fold recognition is a method of
protein modeling which is used to model those proteins which
have the same fold as a proteins of known structure but do not
have homologous proteins with known structure.
• Protein threading is an effective method for identifying the
compatibility of a new protein sequence with a 3D fold that
might not be obvious from normal sequence comparisons.
• It differs from the homology modeling method of structure
predication as it ( protein threading) is used for proteins which
don’t have their homologous protein structure deposited in the
Protein Data Bank(PDB). Whereas homology modeling is used
for those proteins which do.

22. • Threading works by using statistical knowledge of the
relationship between the structures deposited in the PDB and
the sequence of the protein which one wishes to model .
• The prediction is made by "threading" (i.e. placing, aligning)
each amino acid in the target sequence to a position in the
template structure, and evaluating how well the target fits the
template. After the best-fit template is selected, the structural
model of the sequence is built based on the alignment with the
chosen template. Protein threading is based on two basic
observations: that the number of different folds in nature is
fairly small (approximately 1300); and that 90% of the new
structures submitted to the PDB in the past three years have
similar structural folds to ones already in the PDB.

23. Threading

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