Download DOCKING STRUCTURE OF HIV INTEGRASE PROTEIN WITH

Genome to Future Drug
Discovery and Design in
Cancer and Infectious
Diseases
Dr. B.K. Malik
School of Engineering & Technology,
Department of Biotechnology
Sharda University
Greater Noida,UP
DRUG DISCOVERY AND DEVELOPMENT PROCESS CAN BE DIVIDED
INTO SEVERAL PHASES
Phase 1
Safety
Phase 2
Efficacy
Lead compound
Phase 3
Efficacy
Efficacy & selectivity
Drug metabolism & toxicity assessment
2 years
Appropriate target?
2 years
Appropriate selectivity?
Prediction of
Human
Toxicity
4 years
Unanticipated
drug SS
responses
Lack of
efficacy in
some
patients
THE PROCESS OF DRUG DISCOVERY AND DRUG DEVELOPMENT. THROUGHOUT
PROCESS THERE ARE ISSUES WHICH HAVE SIGNIFICANT IMPLICATIONS FOR
SUCCESS OF THE DRUG
TO
DEVELOP
A
PHARMACOGENOMIC
DATABASES FOR ETIOLOGY, INDICATION,
PREVELANCE,CHEMOTHERAPEUTIC
INDICATIONS, CONTRAINDICATIONS AND
DRUG-DRUG INTERACTIONS WITH A VIEW
TO
ESTABLISH
THE
ROLE
OF
PHARMACOGENETIC POLYMORPHISM IN
DIFFERENTIAL
CANCER
DRUG
RESPONSE
IN
AND INFECTIOUS DISEASES
WITH SPECIAL REFERENCE TO THE INDIAN
POPULATION.
DATABASES ADD TO THE KNOWLEDGE OF
DISEASES AND CAN BE USED IN DIFFERENT
WAYS E.g. TO ANALYSE MECHANISMS OR
TO RETRIEVE RETROSPECTIVE AND
PROSPECTIVE INFORMATION ON CLINICAL
PRESENTATION, DISEASE PHENOTYPE,
LONG-TERM PROGNOSIS, AND EFFICACY
OF THERAPEUTIC OPTIONS. THE CLINICAL
INFORMATION MAY BE CRUCIAL FOR THE
DEVELOPMENT OF NEW TREATMENTS
INCLUDING DRUG DESIGN
PREVELANCE OF TUBERCULOSIS
Allergy prevalence is increasing across the World,
including India.
Rising Industrialization and pollution are among
the factors contributing this increase
Currently asthma prevalence in different parts of
India varies between 4% and 20%
The increase in air pollution has been blamed for
the rise in the prevalence of asthma
The International study on Asthma and Allergies
in Children (ISAAC) has also revealed much
higher prevalence in developed countries
compared to South-East Asia.
Cancer of the cervix is the most common cancer
among Women in developing countries.
Rates for this cancer have been declining in
developed countries partly as a result of improved
socio-economic circumstances, better access to
medical facilities and screening.
Cancer of the cervix is the second most common in
Women, comprising 16.6% of all cancers.
It is the most common cancer in black (31.2%) and
colored (22.9%)
Second most common in Asian (8.9%) and fourth
most common in white Women (2.7%)
MTb SYSBORG
DRUG-ACTIVITY QUERY
RESULTS
M Tuberculosis SysBorg
MODELING OF PROTEINS FOR
TUBERCULOSIS
Target
Template
3D STRUCTURE OF Emb A BY MODELLER
RAMACHANDRAN PLOT
Active Site of the EmbA Protein
Docked Structure of EmbA Protein with
UDP-GlcNAc
Emb B PROTEIN MODELING
3D STRUCTURE OF Emb B BY
MODELLER
RAMACHANDRAN PLOT
Active Site of the Emb B Protein
Docked Structure of Emb B Protein with
UDP-GlcNAc
EMB B MUTATED PROTEIN
3D STRUCTURE OF EMB B PROTEIN BY
MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE EMB B MUTATED
PROTEIN
DOCKED STRUCTURE OF EMB B MUTATED
PROTEIN WITH UDP-GlcNAc
Emb C Protein Modeling
Template
Target
3D Structure of Emb C By
Modeller
RAMACHANDRAN PLOT
Active Site of the Emb C Protein
Docked Structure of Emb C Protein with UDPGlc NAC
MODELING OF PROTEINS FOR
DIARRHOEA
TEMPLATE
TARGET
3D Structure of Human Elongation Factor 2
kinase By Modeller
RAMACHANDRAN PLOT
Active Site For Elongation Factor-2kinase Protein
Docked Structure of Human Elongation Factor2-kinase Protein with STAUROSPORINE
HUMAN AFAMIN PRECURSOR
PROTEIN MODELING
Target
Template
3D STRUCTURE OF HUMAN AFAMIN PRECURSOR
BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE HUMAN AFAMIN PRECURSOR
PROTEIN
Docked Structure of Human Afamin Precursor with
MALVIDIN (Natural Ligand)
IHA-HUMAN INHIBIN ALPHA CHAIN PRECURSORHOMOSAPIENS PROTEIN MODELING
3D STRUCTURE OF IHA-HUMAN INHIBIN ALPHA CHAIN PRECURSORHOMOSAPIENS THROUGH MODELLER
RAMACHANDRAN PLOT
Active Site of IHA-HUMAN INHIBIN
ALPHA CHAIN PRECURSOR Protein
Docked Structure of Human Inhibin Alpha Chain with
LEUTEOLIN (Natural Ligand)
HUMAN LONG CHAIN FATTY ACIDCoA LIGASE 5 PROTEIN MODELING
3D STRUCTURTE OF HUMAN LONG CHAIN FATTY
ACID CoA LIGASE 5 BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE HUMAN LONG CHAIN FATTY
ACID CoA LIGASE 5
DOCKED STRUCTURE OF HUMAN LONG CHAIN
FATTYACID CoA LIGASE 5 PROTEIN WITH
PYRAZINAMIDE
Docked Structure of Human Long Chain fatty acid CoA
Ligase 5 Protein with DELPHINIDIN (Natural Ligand)
G-PROTEIN AOUPLED RECEPTRO
CHEMR23 PROTEIN MODELING
TARGET
TEMPLATE
3D STRUCTURTE OF G-PROTEIN AOUPLED
RECEPTRO CHEMR23 PROTEIN BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF G-PROTEIN AOUPLED RECEPTRO
CHEMR23 PROTEIN
DOCKED STRUCTURE OF G-PROTEIN AOUPLED
RECEPTRO CHEMR23 PROTEIN WITH AMYLOID BETA
PEPTIDE
Docked Structure of G-PROTEIN AOUPLED
RECEPTRO CHEMR23 PROTEIN with CYANIDIN
(Natural Ligand)
MODELLING OF PROTEINS FOR
HIV
TARGET
TEMPALTE
3D STRUCTURE OF HIV INTEGRASE OBTAINED
THROUGH MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE FOR HIV INTEGRASE PROTEIN
DOCKING STRUCTURE OF HIV INTEGRASE PROTEIN
WITH FLAVOPIRODOL (Natural Ligand)
DOCKING STRUCTURE OF HIV INTEGRASE
PROTEIN WITH QO2793(SMALL PEPTIDE)
MUTATED HIV INTEGRASE
3D STRUCTURE OF MUTATED HIV INTEGRASE
RAMACHANDRAN PLOT
ACTIVE SITE FOR MUTATED HIV INTEGRASE
Docked structure of MUTATED HIV INTEGRASE with
FLAVOPIRIDOL (Natural Ligand)
DOCKED STRUCTURE MUTATED HIV INTEGRASE
WITH 1QCJB(SMALL PEPTIDE)
GAG-POL POLYPROTEIN
3D STRUCTURE OF GAG-POL POLYPROTEIN BY
MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE GAG-POL POLY PROTEIN
DOCKED STRUCTURE OF GAG-POL POLY
PROTEIN WITH RO 31-8959(CHEMICAL LIGAND)
Docked structure of HIV Gag-Pol Polyprotein and
2BDS(SMALL PEPTIDE)
MUTATED GAG-POL POLYPROTEIN
ACTIVE SITE OF THE MUTATED GAG-POL POLY
PROTEIN
Docked structure of Mutated HIV Gag-Pol Protein
and Abrelix
Docked structure of Mutated HIV Gag-Pol Polyprotein
and Q40772(Small Peptide)
MODELING OF PROTEINS FOR NEUROLOGICAL
DISORDERS
ACY2_HUMAN ASPARTOACYLASE
3D STRUCTURE OF ACY2_HUMAN ASPARTOACYLASE
BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE ACY2_HUMAN
ASPARTOACYLASE
DOCKED STRUCTURE OF ACY2_HUMAN ASPARTOACYLASE
WITH D-ASPARTIC ACID
CAH3_HUMAN Carbonic anhydrase
Protein Modeling
3D STRUCTURE OF CAH3_HUMAN Carbonic
anhydrase Protein BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE CAH3_HUMAN Carbonic
anhydrase Protein
DOCKED STRUCTURE OF CAH3_HUMAN Carbonic
anhydrase Protein WITH ACETAZOLAMODE
GAMMA-AMINOBUTYRIC ACID(GABA) A
RECEPTOR PROTEIN MODELING
Target
Template
3D STRUCTURE OF gamma-aminobutyric acid
(GABA) A receptor BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE gamma-aminobutyric acid
(GABA) A receptor
DOCKED STRUCTURE OF gamma-aminobutyric
acid (GABA) A receptor WITH GABACULINE
GLUTAMATE TRANSPORTER
3D STRUCTURE OF GLUTAMATE TRANSPORTER BY
MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE GLUTAMATE
TRANSPORTER
DOCKED STRUCTURE OF GLUTAMATE TRANSPORTER
WITH LIDOCANE
GBRA6_HUMAN Gamma-aminobutyric-acid
receptor alpha-6 subunit precursor
3D STRUCTURE OF GBRA6_HUMAN Gamma-aminobutyric-acid
receptor alpha-6 subunit precursor BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE GBRA6_HUMAN Gammaaminobutyric-acid receptor alpha-6 subunit precursor
DOCKED STRUCTURE OF GBRA6_HUMAN Gammaaminobutyric-acid receptor alpha-6 subunit precursor WITH
FELBAMATE
MODELING OF PROTEINS FOR BREAST CANCER
TUBULIN BETA-1 CHAIN PROTEIN
3D STRUCTURE OF 2BTOA BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE 2BTOA PROTEIN
DOCKED STRUCTURE OF TUBULIN BETA-1 CHAIN
PROTEIN WITH CALPHOSTIN-I (chemsketch)
DOCKED STRUCTURE OF TUBULIN BETA-1 CHAIN
PROTEIN WITH 2BDS
(small poly-peptide)
MUTATED TUBULIN BETA-1 CHAIN
PROTEIN
3D STRUCTURE OF 10FUA BY MODELLER
RAMACHANDRAN PLOT
ACTIVE SITE OF THE 1OFUA PROTEIN
DOCKED STRUCTURE OF MUTATED TUBULIN BETA-1
CHAIN PROTEIN WITH CALPHOSTIN-I (chemsketch)
DOCKED STRUCTURE OF MUTATED TUBULIN BETA-1
CHAIN PROTEIN WITH 2BDS
(small poly-peptide)
CONCLUSION

THE DATABASES MODEL PRESENTED AND APPLIED HERE WILL
ALSO BE USEFUL FOR THE ANALYSIS OF THE GENES TO BE
FOUND TOGETHER ALL THESE DATABASES ADD CONSIDERABLY
TO OUR KNOWLEDGE ABOUT MECHANISMOF ACTION, DRUGDRUG INTERACTION, IMMUNODEFECIENCIES, GENETICS, AND
TREATMENT.

PHARMACOGENOMIC DATA BASES TOOLS CAN BE APPLIED
TO DRUG DEVELOPMENT WITH THE AIM TO INCREASE THE
EFFICIENCY OF THE PROCESS AND THE QUALITY OF PRODUCT.

IT MAY BE CONCLUDED THAT MODELS OF PROTEINSOF
DIFFERENT DISEASES SHALL HELP IN UNDERSTANDING DISEASE
PROCESSES AND DRUG DESIGN.