Basic introduction about Protein structure prediction and its computational resources.....

1. Presented by
Er. Ritesh Kumar
Department of Biotechnology
er.riteshkumar007@gmail.com
Biotechnology – 3rd Year

2. PROTEIN STRUCTURE PREDICTION
• One of the key challenges in protein science is
determining three dimensional structure from
amino acid sequence.
• Although experimental methods for determining
protein structures are providing high resolution
structures, they cannot keep the pace at which
amino acid sequences are resolved on the scale of
entire genomes.
• Various computational tools have been developed
that predict different levels of protein structural
hierarchy.

3. • The starting point (input) of protein structure prediction is the
one-dimensional amino acid sequence of target protein and the
ending point (output) is the model of three-dimensional
structures.
• Proteins are chains of amino acids joined by peptide bonds.
• The 20 amino acids found in proteins can be grouped
according to the chemistry of their R groups.
• The R side chains also play an important structural role.
• Special roles are played by glycine, which does not have a side
chain and can therefore increase local flexibility in structures,
and cysteine, which can react with another cysteine to form a
cross-link that can stabilize the protein structure
PROTEIN STRUCTURE PREDICTION

4. • In these secondary structures, regular patterns of H bonds are
formed between neighboring amino acids, and the amino acids
have similar Φ and ψ angles.
• The secondary structures are tightly packed in the protein core
in a hydrophobic environment.
• Determining the structure of a protein can be achieved by
time-consuming and relatively expensive techniques such as
crystallography, nuclear-magnetic resonance spectroscopy, and
dual polarization interferometry.
PROTEIN STRUCTURE PREDICTION

6. • α-Helix:-
– The helix depicted is the most abundant type of secondary structure in
proteins. The helix has 3.6 amino acids per turn with an H bond formed
between every fourth residue; the average length is 10 amino acids (3
turns) or 10 Å but varies from 5 to 40 (1.5 to 11 turns).
– Regions richer in alanine (A), glutamic acid (E), leucine (L), and
methionine (M) and poorer in proline (P), glycine (G), tyrosine (Y),
and serine (S) tend to form an helix.

7. β-Sheet
• Sheets are formed by H
bonds between an
average of 5–10
consecutive amino acids
in one portion of the
chain with another 5–10
farther down the chain.

8. Loop
• Loops are regions of a protein chain that are (1) between
helices and sheets, (2) of various lengths and three-
dimensional configurations, and (3) on the surface of the
structure.
• Loops also tend to have charged and polar amino acids and are
frequently a component of active sites.
Coil
• A region of secondary structure that is not a helix, a sheet, or a
recognizable turn is commonly referred to as a coil

9. • To understand how a protein gets its final
shape or conformation, we need to understand
the four levels of protein structure:
– primary
– secondary
– Tertiary, and
– Quaternary.
LEVELS OF PROTEIN STRUCTURE

11. Primary structure
• The simplest level of protein structure, primary
structure, is simply the sequence of amino acids
in a polypeptide chain. For example, the hormone
insulin has two polypeptide chains, A and B,
shown in diagram below.
• Each chain has its own set of amino acids,
assembled in a particular order. For instance, the
sequence of the A chain starts with glycine at the
N-terminus and ends with asparagine at the C-
terminus, and is different from the sequence of the
B chain.

12. • The next level of protein structure, secondary
structure, refers to local folded structures that form
within a polypeptide due to interactions between atoms
of the backbone. (The backbone just refers to the
polypeptide chain apart from the R groups – so all we
mean here is that secondary structure does not involve
R group atoms.)
• The most common types of secondary structures are the
α helix and the β pleated sheet. Both structures are held
in shape by hydrogen bonds, which form between the
carbonyl O of one amino acid and the amino H of
another.
Secondary structure

13. • The overall three-dimensional structure of a polypeptide is
called its tertiary structure. The tertiary structure is primarily
due to interactions between the R groups of the amino acids
that make up the protein.
• R group interactions that contribute to tertiary structure
include hydrogen bonding, ionic bonding, dipole-dipole
interactions.
• Also important to tertiary structure are hydrophobic
interactions, in which amino acids with nonpolar, hydrophobic
R groups cluster together on the inside of the protein.
Tertiary structure

14. • Many proteins are made up of a single
polypeptide chain and have only three levels of
structure (the ones we’ve just discussed).
However, some proteins are made up of
multiple polypeptide chains, also known as
subunits. When these subunits come together,
they give the protein its quaternary
structure.
Quaternary structure

15. Computational Resources for Protein
Structure prediction
To be continued..........