Structural Bioinformatics - bio-bio-1

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2 Οκτ 2013 (πριν από 3 χρόνια και 2 μήνες)

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S
TRUCTURAL

B
IOINFORMATICS

S
TRUCTURAL

B
IOINFORMATICS


A subset of Bioinformatics concerned with the of
biological structures
-

proteins, DNA, RNA,
ligands

etc.


It is the first major effort to show the application of
Bioinformatics on


Macromolecular structure prediction,


How macromolecules carry out cellular functions,


How bioinformatics can improve health care system by
accelerating diagnostic procedure of diseases and drug
discovery.

D
ISCOVERY

A
ND

D
ESIGN

OF

D
RUGS

Traditional

Methods

Modern

Method of Drug Discovery/

Rational Drug

Design


It is one of the most promising area of application for
Bioinformatics research.


The process of drug discovery involves


Identification,


Synthesis,


Characterization,


Screening, and


Assay of candidates for therapeutic efficacy.



So this is the end
-
to
-
end process of designing
pharmaceutical agents to prevent and/or cure human
disease

S
TRUCTURAL

B
IOINFORMATICS

IN

D
RUG

D
ISCOVERY

I
NTERESTING

FACTS
...


Over 90% of drugs
entering clinical
trials fail to make it
to market


The average cost to
bring a new drug to
market is estimated
at
$770 million

I
MPACT

OF

S
TRUCTURAL

B
IOINFORMATICS


ON

D
RUG

D
ISCOVERY


Speeds up key steps in Drug
discovery process by
combining


bioinformatics,


structural biology, and


structure
-
based drug design

I
DENTIFYING

T
ARGETS

Human Genome

polysaccharides

lipids

nucleic acids

proteins


Toxicity, specificity and difficulty in designing
Potent Inhibitor……eliminate


Polysaccharides


Lipids


Nucleic acids

Human Genome

proteins

Proteins
with
Binding Site

Protein:

Ion channels

Receptors

Enzymes

R
ELATING

TARGETS

TO

DISEASE
...



Analysis of
Pharma


industry reveals:



Over 400 proteins used as
drug targets



Sequence analysis of these
proteins shows that most
targets fall within a few
major gene families
(GPCRs
-

Guanine Nucleotide
Binding
-
Protein Coupled
Receptors
,
kinases
,
proteases and peptidases)



Fig.

Fauman

et al.

Drug Design

Structure based

Ligand

based

Ligand

(
analog) based
drug
design




Receptor
structure is not known



Mechanism
is known/ unknown



Ligands

and their biological
activities
are known

Target (structure) based
drug design




Receptor
structure is known



Mechanism
is known



Ligands

and their biological
activities are known/ unknown

B
RINGING

A

N
EW

D
RUG

TO

M
ARKET

Review and approval by Food
& Drug Administration

1
compound
approved

Phase III
: Confirms effectiveness and monitors
adverse reactions from long
-
term use in 1,000 to

5,000 patient volunteers.

Phase II:

Assesses effectiveness and
looks for side effects in 100 to 500 patient
volunteers.

Phase I:

Evaluates safety and dosage


in 20 to 100 healthy human volunteers.

Discovery and preclininal testing:

Compounds are identified and evaluated
in laboratory and animal studies for
safety, biological activity, and formulation.

5,000 compounds
evaluated

0

2

4

6

8

1
0

12

14
Years


16

Source: Tufts Center for the Study of Drug Development