Bioinformatics

Molecular Biology- 2
 Bioinformatics as
Genomics and Proteomics
• Genomics deals with biological questions from the
perspective of the whole genome

• Analysis of proteins, genes and genomes using computer

algorithms and computer databases

• Biology is an information science

• Interface of biology (information) and computers

(algorithms) = bioinformatics

• The tools of bioinformatics enable the field of genomics and

proteomics
 Biologists:
Constructing
interesting questions
and working with
Biologists CS to design
QUESTIONS
algorithms to address
the questions
ALGORITHM
DESIGN
CompSci:
PROGRAMMING
Working with
biologists to design
algorithms and
construct ways to
Computer scientists
implement them
 Fundamental Process in Biology

DNA RNA protein phenotype

 DNA
• Deoxyribo-nucleic acid, called DNA for short, is the
biomolecule that is most responsible for providing a living
organism with a way to store and express the information for
life

• It is also the medium by which genetic information is

transferred from a parent to its offspring

• Encoded upon the DNA strands are regions (also known as

genes) with discrete instructions for producing the molecular
tools required for all living organisms - namely proteins
 Proteins

• The proteins that are produced have functional roles in just about
every aspect of a living cell.

– Some proteins play a structural role in a cell

– Other proteins are enzymes that regulate many biochemical

pathways in living organisms

• The process of taking the genetic information and converting it to

a protein, of which DNA plays an important role, is a fairly
complicated process
 Structure of DNA
• DNA, is a nucleic acid molecule that contains the genetic
instructions used in the development and functioning of all
known living organisms

• It is often considered as a set of blueprints, since DNA contains

the instructions needed to construct other components of
cells, such as proteins and RNA molecules

• The DNA segments that carry this genetic information are

called genes
 Structure of DNA
• Chemically, DNA is a long polymer of simple units called
nucleotides, with a backbone made of sugars and
phosphate atoms joined by ester bonds

• Attached to each sugar is one of four types of molecules

called bases

• It is the sequence of these four bases along the backbone

that encodes information
Nucleic Acids
• Nucleic acids are polynucleotides
made up of individual nucleotides
linked together

• A nucleotide can itself be further

broken down to yield three
components:
a sugar,
a Nitrogen (amine) base, and
phosphoric acid.
Adenosine and guanosine are both purines, and thymidine and cytidine are pyrimidines. A pairs with T, and G
pairs with C.

http://www.sciencetechnologies.com/examples/example7/example7/index.html
STRUCTURE OF NUCLEIC ACID CHAINS

• Nucleotides are joined together in DNA and RNA

by phosphate ester bonds between the phosphate
component of one nucleotide and the sugar
component of the next nucleotide

• An ester bond is a bond which occurs between a

Carbon atom and an Oxygen atom.

http://www.sciencetechnologies.com/examples/example7/example7/index.html
Poly-nucleotide Chain

• More and more nucleotides can be added on

by the same process of forming ester bonds
until an immense chain is formed.

• But no matter how long a polynucleotide chain

is, one end of the nucleic acid molecule always
has a free -OH group on the sugar at the
Carbon known as C3' (called the 3' end) and the
other end of the molecule always has a
phosphoric acid group at C5' (the 5' end).

http://www.sciencetechnologies.com/examples/example7/example7/index.html
Formation of Nucleic Acid

• Repeating the above step several thousands of times will

yield a nucleic acid

• This process is not at all random, there is a high degree

of order in the manner to which DNA is assembled

• This is because a gene is actually a specific sequence (or

groups of sequences) of bases on one strand that either
defines a single protein (structural gene), or an RNA that
serves an important function without coding for a protein
(such as transfer RNA or ribosomal RNA)

• Enzymes regulate and mediate the activities

DNA
Strand is
antiparallel
Watson and Crick - The
Double Helix

• In late 1953, James Watson and

Francis Crick presented a model of
the structure of DNA

• It was already known from

chemical studies that DNA was a
polymer of nucleotide (sugar, base
and phosphate) units
 https://web.chemdoodle.com/kekules-dream/

https://www.ted.com/talks/james_watson_on_how_he_discovered_dna

http://www.wiley.com/legacy/college/boyer/0470003790/animations/animations.htm
Nobel Prize awarded research
Paper in Nature
The Central Dogma
 Living Systems and the Central Dogma

• Living systems
– What are the properties of a living system?

• Central Dogma demystified

– Why is it DNA to RNA to protein?
– What is the role of each of these three things?

• The goal today is not to learn the details, but to

appreciate why the details are interesting and
important
 What are some universal properties of
living systems?
• Must build and run the cell

• Must acquire energy to do so

• Must respond to the environment

• Must reproduce
 Central Dogma

• The mechanism by which all of this happens is

encapsulated in the Central Dogma

• flow of information from DNA to RNA to

proteins

• This is the system that earth life has settled on

 Why do we care about these 3 things?
DNA, RNA, protein
PROTEINS
• What is it about proteins that is important to life?
– What are the functions of proteins?
• Machinery that does stuff
• Builds the membrane that encloses cells
• Breaks down food to provide fuel
• Receives information from the environment and
communicates it to the cell so that the cell can respond
• If all these parts and machinery are not made, life
does not exist
 Why do proteins serve as the machinery/parts?
• Proteins = diversity
– Chains of 20 different amino acids, with
a WIDE range of biochemical properties

– This allows two things

• Diversity in how proteins fold into 3
dimensional structures
• Diversity in the types of chemical
interactions they have with other
molecules
– Enzymes catalyze reactions by bringing
two molecules together and facilitating
changes in chemical bonds
– Structural proteins maintain appropriate
shapes to facilitate structures
 Protein

• Proteins form a diversity of shapes and

chemical properties
• Proteins are great at serving as machines and
as building materials
 DNA - Revisited

• What is the significance of DNA?

– It is the permanent set of instructions of what
proteins to make = genes
– It also contains instructions on WHEN to make the
proteins = regulatory regions
– And other stuff
 Nucleic acids v proteins
• Nucleic acids
– Polymers (strings) of just 4 nucleotides: the bases are all chemically similar
– Base pairing between two DNA strands creates a 3 dimensional structure
– Hydrogen bonding is the primary chemical interaction
– Base pairing allows for a way to create exact copies
 Take home: DNA
• Nucleic acids are very stable and can produce
exact replicas of themselves
– Double strands separate
– Each single strand serves as a template to build a
complementary copy to produce 2 dsDNA
– Proteins cannot do this.

DNA is GREAT at carrying information through time

 DNA vs protein

• DNA is a polymer of nucleotides

• Protein is a polymer of amino acids

• Nucleotides have VERY different chemical

properties than amino acids
• So polymers of nucleotides (nucleic acids)
have very different properties than polymers
of amino acids (proteins)
 From DNA to protein
• DNA serves as a way to store information through time, through
generations
• This could include information about when and how to build proteins

• Protein serves as a way to build all the components of cells, and to

run them
• Including helping DNA replicate itself so that it can be passed down to
a new generation of cells

• If DNA stores information about what proteins to make, and the

proteins build the cell, what is the process for translating from DNA
language (nucleotides) into protein language (amino acids)?

• Now we can think about the role of RNA

– RNA allows the instructions to be read and the proteins to be built
– It translates the language of DNA (nucleotides) into the language of
proteins (amino acids)
 RNA
• The cell needs a process to
– Read the instructions
– Translate the encoded DNA instructions into the
building blocks of proteins
– Build the proteins

• RNA does all of this

– Read instructions mRNA
– Translate DNA to AA tRNA
– Build proteins rRNA
translation
 mRNA

• Messenger RNA
– A copy of the gene sequence that is mobile and
can be carried to the site of protein synthesis

RNA is a nucleic acid, like DNA. However

DNA = A T C G
RNA = A U C G
 The Synthesis of Proteins

• Instructions for generating Amino Acid sequences

– (i) DNA double helix is unzipped
– (ii) One strand is transcribed to messenger RNA
– (iii) RNA acts as a template
• ribosomes translate the RNA into the sequence of amino
acids
• Amino acid sequences fold into a 3d molecule
• Gene expression
– Every cell has every gene in it (has all chromosomes)
– Which ones produce proteins (are expressed) & when?
 Transcription

• Take one strand of DNA

• Write out the counterparts to each base
– G becomes C (and vice versa)
– A becomes T (and vice versa)
• Change Thymine [T] to Uracil [U]
• You have transcribed DNA into messenger RNA
• Example:
Start: GGATGCCAATG
Intermediate: CCTACGGTTAC
Transcribed: CCUACGGUUAC
 Genetic Code

• How the translation occurs

• Think of this as a function:

– Input: triples of three base letters (Codons)
– Output: amino acid
– Example: ACC becomes threonine (T)

• Gene sequences end with:

– TAA, TAG or TGA
Genetic Code
A=Ala=Alanine
C=Cys=Cysteine
D=Asp=Aspartic acid
E=Glu=Glutamic acid
F=Phe=Phenylalanine
G=Gly=Glycine
H=His=Histidine
I=Ile=Isoleucine
K=Lys=Lysine
L=Leu=Leucine
M=Met=Methionine
N=Asn=Asparagine
P=Pro=Proline
Q=Gln=Glutamine
R=Arg=Arginine
S=Ser=Serine
T=Thr=Threonine
V=Val=Valine
W=Trp=Tryptophan
Y=Tyr=Tyrosine
 Example Synthesis
• TCGGTGAATCTGTTTGAT
Transcribed to:
• AGCCACUUAGACAAACUA
Translated to:
• SHLDKL