Structural & Functional

Bioinformatics
Lecture 1

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Bioinformatics
Biological Computer
Data + Calculations

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What is Bioinformatics?
(Molecular) Bio – informatics

One idea for a definition?

Bioinformatics is conceptualizing biology in terms of
molecules (in the sense of physical-chemistry) and
then applying “informatics” techniques (derived from
disciplines such as applied math, CS, and statistics) to
understand and organize the information associated
with these molecules, on a large-scale.

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In biology, Bioinformatics is an interdisciplinary field
that develops and improves on methods for storing,
retrieving, organizing and analyzing biological data.

 A major activity in bioinformatics is to develop

software tools to generate useful biological knowledge.

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 Structural Bioinformatics
This branch of bioinformatics is concerned with computational
approaches to predict and analyze the spatial structure of proteins
and nucleic acids.

Structural Bioinformatics is a practical discipline with many

applications that deal with biological three dimensional structural
data.

Structural bioinformatics is computer aided structural biology!

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 Nucleic acid structure

Nucleic acid structure refers to the structure of nucleic

acids such as DNA and RNA. Chemically speaking,
DNA and RNA are very similar.

Nucleic acid structure is often divided into four

different levels primary, secondary, tertiary and
quaternary.

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Protein Structure
Protein structure is the bimolecular structure of
a protein molecule. Each protein is a polymer –
specifically a polypeptide – that is a sequence formed
from various amino acids (also referred to as
residues). 

Protein structures range in size from tens to several

thousand residues.

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Why should we care?

Because biomolecules are “nature’s robots” [Tanford,

2001]

… and because it is only by coiling into specific 3D
structures that they are able to perform their functions

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Protein Structure
Proteins consist of amino acids.

Polypeptide chains fold into specific 3D structures.

Function is performed by the folded protein.

Proteins are dynamic and only marginally stable.

In evolution structure is conserved longer than both

function and sequence.
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Why are Protein Structures so Interesting?
They provide a detailed picture of interesting biological
features, such as active site, substrate specificity, allosteric
regulation etc.

 They aid in rational drug design and protein engineering.

 They can elucidate evolutionary relationships

undetectable by sequence comparisons.

They can be used to put mutations in the proper

structural context.
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 Why Proteins Structure ?
 Proteins are fundamental components of all living
cells, performing a variety of biological tasks.

 Each protein has a particular 3D structure that

determines its function.

 Protein structure is more conserved than protein

sequence, and more closely related to function.

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Proteins perform most essential biological and
chemical functions in a cell. They play
important roles in structural, enzymatic,
transport, and regulatory functions.

The protein functions are strictly determined

by their structures. Therefore, protein
structural bioinformatics is an essential
element of bioinformatics.

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 Protein Structure
Protein core - usually conserved.

Protein loops - variable regions

Surface loops

Hydrophobic core

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Principles of Protein Structure
•Today's proteins reflect millions of years of
evolution.

•3D structure is better conserved than sequence

during evolution.

•Similarities among sequences or among structures

may reveal information about shared biological
functions of a protein family.

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 Structure – Sequence Relationships

• Two conserved sequences similar structures

• Two similar structures ? conserved sequences

There are cases of proteins with the same

structure but no clear sequence similarity.

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Assignment # 1 (Due on September 18 in class)

Define and Explain the following four roles of proteins

with examples:
Structural
Enzymatic
Transport &
Regulatory functions

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 Structural alignment
 Structural similarity can point to remote
evolutionary relationship

 Shared structural motifs among proteins suggest

similar biological function

 Getting insight into sequence-structure mapping

(e.g., which parts of the protein structure are
conserved among related organisms).

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If using structure information two basic approaches
are possible:

 (1) aligning the sequences, and

(2) “structural alignment” which compares the

structures to one another and ignores the type of
amino acid at a certain position.

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Protein Basics:
Proteins are macromolecules

Amino acids are the basic building blocks of proteins

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Amino Acids are classified by properties: polar, non
polar, and charged (ionic)

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Polypeptides are constructed by condensation reactions
with amino acids

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Protein Architecture
Proteins are polymers consisting of amino acids linked by
peptide bonds
each amino acid consists of
– a central carbon atom (alpha-carbon)
– an amino group, NH2
– a carboxyl group, COOH
– a side chain
 differences in side chains distinguish different amino
acids

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Amino acids can be grouped into several categories based on the
chemical and physical properties of the side chains, such as size and
affinity for water.

According to these properties, the side chain groups can be divided

into small, large, hydrophobic, and hydrophilic categories. Within
the hydrophobic set of amino acids, they can be further divided into
aliphatic and aromatic. Aliphatic side chains are linear hydrocarbon
chains and aromatic side chains are cyclic rings. Within the
hydrophilic set, amino acids can be subdivided into polar and
charged.

Charged amino acids can be either positively charged (basic) or

negatively charged (acidic).

Each of the twenty amino acids, their abbreviations, and main

functional features once incorporated into a protein are listed in
Table
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Amino Acids and Peptide Bonds
side chains vary in
– shape
– size
– charge
– polarity

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