COMPUTATIONAL BIOLOGY

ENS 210

Spring Semester
2012

Faruk Berat AKCESME MSc

 Office F 1.35

GSM: +387 62 761 196

fakcesme@ius.edu.ba

All homework and questions must be submitted

by email to iuscombio@yahoo.com
COMPUTATIONAL BIOLOGY

The development and application of data analytical and

theoretical methods, mathematical modeling and
computational simulation techniques to the study of biological,
behavioral, and social systems.
 Centers/Institutions and leading providers of
Computational Biology Resources
• National Center for Biotechnology Information (NCBI)

• European Bioinformatics Institute (EBI)

• Swiss Institute of Bioinformatics (SIB)

• European Molecular Biology Laboratory (EMBL)

• Welcome Trust Sanger Institute (WTSI) or The Sanger

• Broad Institute

• Whitehead Institute

• The Institute for Genomic Research

• Center for Biomolecular Science and Engineering

• Netherlands Bioinformatics Centre

• COSBI - The Centre for Computational and Systems Biology

• DLab - Computational Biology Lab (Chile)

• Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG)
COMPUTATIONAL BIOLOGY

BIOINFORMATICS
GENOMICS

STRUCTURAL PROTEOMICS
GENOMICS

COMPUTATIONAL MOLECULAR BIOLOGY

COPMUTATIONAL BIOLOGY
 Computational Biology vs. Bioinformatics

• Computational Biology uses mathematical and computational

approaches to address theoretical and experimental questions in
biology.

• Bioinformatics applies principles of information sciences and

technologies to make the vast, diverse, and complex life sciences
data more understandable and useful.

Although bioinformatics and computational biology are distinct,

there is also significant overlap and activity at their interface.
Another opinion is that Bioinformatics encompasses anything to do
with analysis, visualization and management of biological
sequences, while Computational Biology refers to Bioinformatics
plus everything else that involves computers in the solving of
biological problems.

Some biological areas that involve computation:

– Mathematical modeling of ecosystem
– Population dynamics
– Application of the game thoery in behavioral studies.
– Phylogenetics constructions.
COMPUTATIONAL BIOLOGY

BIOINFORMATICS
GONOMICS
SYSTEM BIOLOGY

STRUCTURAL PROTEOMICS
GENOMICS

COMPUTATIONAL MOLECULAR BIOLOGY

COPMUTATIONAL BIOLOGY
COMPUTATIONAL BIOLOGY
 INDIVIDUALS

RNA PROTEIN

DNA PHENOTYPE

EVOLUTION SELECTION

POPULATIONS

BIOLOGICAL INFORMATION
BIOINFORMATICS
COMPUTATIONAL GOALS FOR
BIOINFORMATICS
CENTRAL PARADIGM OF MOLECULAR
BIOLOGY
CENTRAL PARADIGM OF
BIOINFORMATICS
 Challenges Understanding
Genetic Information

• Genetic information is redundant.

• Structural information is redundant.
• Genes and proteins are meta-stable.
• Single genes have multiple functions.
• Genes are one dimensional but function depends on three-
dimensional structure.
 MOLECULAR BIOLOGY
• SOME ORGANIC CHEMISTRY
– SMALL MOLECULES

– SUGAR

– NUCLEIC ACIDS
• NUCLEOTIDES

• DNA

• RNA
 SOME ORGANIC CHEMISTRY
1. Carbon can fill its outer energy level by forming 4 single
A carbon atom contains 6
covalent bonds with other atoms protons, 6 neutrons, and 6
2. Carbon is outstanding among all of the elements on electrons, 2 in the first energy
level and 4 in the second
earth because of its ability to form large molecules.

i) by forming covalent bonds with other carbon atoms

ii) by forming covalent bonds with oxygen, nitrogen,
phosphorus, and sulfur
iii) by forming chains of unlimited length by bonding
with other carbon atoms or by forming rings.
 It is possible to build large, stable
molecules using carbon!!
• Covalent bond • Non-covalent bonds
Formed between • Hydrogen
two atoms that • Ionic
share electrons • Van der Vaals
 HYDROGEN BONDS!
Hydrogen
• Hydrogen bonds are used for base pairing, which hold bonds

together the two strands of the DNA double helix.

• Also play an important in RNA as well as in stabilizing

protein structure

• A hydrogen bond can be formed if there are two

electronegative atoms (such as oxygen or nitrogen) that

share a hydrogen atom.

 SMALL MOLECULES!
• A cell is made up of small number of elements C, N,O and H
make up 99% of the mass. Hydrocarbon molecule consist of only
carbon and hydrogen.

• Some specific simple groups such as the

– hyroxyl group –OH

– The carboxyl group –COOH (organic acid)

– Amino group –NH 2 commonly (organic molecules)

• Another important class of C-O compounds are generated by an ester linkage.

• Small molecules are defined as organic molecules with up to 30 carbon atoms.

• A macromolecule, which is composed of number of euqal or similar smaller molecules, is

calles polymer.

• The most important polymers are DNA ,RNA (composed of nucleotides) and proteins

(composed of amino acids)

 Four groups of small molecules
• Sugar: A sugar molecule is a small carbonhydrate Cx(H2O)y, larger
are called polysaccharides.

• Fatty acids: componenets of lipid molecules.

• Nucloties: building blocks for DNA and RNA.

• Amino acids: molecules containing an amine group, a carboxylic

acid group, and a side-chain that is specific to each amino acid.
 Sugars
• Sugars can be distinguished with respect to their number of carbon atoms and with respect of their
molecular structure.
– Pentoses-having 5 Cs
Since the keto or aldehyde group can react
– Hexoses-having 6 Cs with a hydroxyle group, a sugar can occur
With respect to structure in cyclic form
Aldehyde sugars /ketone sugars
5 carbon sugars calles ribose in molecular biology!
there are two different forms of ribose
• Ribose
• Deoxyribose –one exygen atom is missing
 Nucleotides
• Both DNA and RNA are polymers, which
composed of nucleotides (nucleotide
polymers ar also called oligonucleotides)

• A nucleotide is a molecule consisting of a

base, a ribose sugar (in DNA
deoxyribose) and a phospate molecule.

• The base is a carbon ring molecule

containing nitrogen atoms.
• In DNA we have the four bases adenine (A), cytosine (C), guanine (G), and

thymine (T). In RNA, the thymine is replaced by uracil (U). The purines (adenine

and guanine) have a 2-ring structure, and pyramidines (cytosine,thymine and uracil)

kave a 1 ring structure.

• Adenine and thyime have 2 hydrogen bond sites whereas cytosine and guanine have

3 hydorgen bond sites.

 DNA!
At the room temprature DNA exist as a double-
stranded molecule, formed by hydrogen bonds
between complementary bases: A with T, and C with
G (called Watson-Crick rules)
 RNA!
• Ribonucleic acid (RNA) consist of bases adenine, cyotine,

guanine, and uraci (in place of thymine) attached in a similar

manner to pentose sugar ribose.

• Ribose has an extra hydroxyl (OH) group at the 2’ position, so is

able to form more hydrogen bonds than DNA.

• In contrast to DNA, RNA is single stranded, forming hairpin

loops and more complicated structure.

– mRNA: transcribed from a DNA template, and carries coding

information to the sites of protein synthesis: the ribosomes

– tRNA: a small RNA chain of about 80 nucleotides that transfers a

specific amino acid to a growing polypeptide chain at the ribosomal

site of protein synthesis during translation

– rRNA: catalytic component of the ribosomes

 RNA splicing!
Splicing is a modification of an RNA after transcription, in

which introns are removed and exons are joined. This is needed for

the typical eukaryotic messenger RNA before it can be used to

produce a correct protein through translation.

 Proteins!
Amino acids

• Proteins are sequences composed

of an alphabet of 20 amino acids.

• There are 20 different chain

residues, which have different

chemical properties. Residues

can be hydrophobic or

hyrophilic, small or large, Where R is a chemical group specifying the type of

the amino group, and the left COOH the carboxyl
charged or uncharged. group.
Using the peptide bond, long chains of
amino acids can be generated.
Two amino acids can
be connected via a
peptide bond, where
the carboxyle group of
the first amino acid
reacts with the amino
group of the second.
A molecule of
water removed
• Amino acid have numerous
different chemical proporties.
Molecular size, electric charge.
• The 20 amino acids have 1-letter
and 3-letter codes.
• The genetics code is now known to
be a triplet, non overlapping, where
successive codons consisting of 3
successive RNA nucleotides encode
one of the 20 amino acids. For
instance:
 Protein Structure
• The function of a protein is determined by its 3-dimensional structure.

• Example: antibodies in the human immune system recognize antigens

by having a complementay surface to that of the antigen (key and lock

paradigm).
 Protein Structure
• Protein may roughly be divided into three classes: globular
(enzymes), fibril (collagen, elastin), and membrane proteins.
• Primary structure: the amino acid sequence of the
protein.

• Secondary structure: highly regular local sub-

structures / describes the regions in the primary
structure where secondary structure elements
occur.

Tertiary structure: the 3-dimensional structure of a protein

domain in the native structure.

Quarternary structure: the 3-dimensional,

native structure of the fully functional protein.
 From DNA to protein
• There are two steps to
making proteins from
DNA.

• The first step is called

transcription. This is
where you go from the
DNA to and mRNA
strand.

The next step is translation. This is where the mRNA moves to the ribosomes and tRNA
brings amino acids in the correct sequence.
 Transcription
Transcription is when the code from a
DNA sequence is used to make a
complementary strand of mRNA.

For example if your DNA strand was

AGTTCGA the mRNA that would be
made from that strand is
UCAAGCU. A goes with U and G
goes with C in RNA.

http://www.dnatube.com/video/3450/DNA-Transcription
• Transcription is the first step leading to gene expression. The stretch of DNA transcribed into
an RNA molecule is called a transcription unit and encodes at least one gene.

• If the gene transcribed encodes a protein, the result of transcription is messenger

RNA (mRNA), which will then be used to create that protein via the process of translation.
Alternatively, the transcribed gene may encode for either ribosomal RNA (rRNA) or transfer
RNA (tRNA), other components of the protein-assembly process, or other ribozymes.
 Translation
Translation is when the
mRNA moves to the
ribosomes and tRNA
molecules bring amino acids
to the mRNA by every three
bases, called codons. Use a
codon chart to find out what
amino acids match with the
mRNA sequence.

Go and make your own mRNA

http://learn.genetics.utah.edu/content/begin/dna/transcribe/
The different models of transcription and translation in prokaryotes and eukaryotes.
The end of the first week!!