This document discusses molecular design and computer-aided molecular design. It covers topics like medicinal chemistry applied to diseases, designing new enzyme inhibitor drugs like doxorubicin. Natural products chemistry and examples like penicillin and taxol are also mentioned. Principles of molecular recognition involving hydrogen bonding, charge interactions, and hydrophobic effects are summarized. Computer-aided molecular design techniques like quantitative structure-activity relationships are also discussed. Specific examples involving acetylcholine esterase and using log P values to understand hydrophobicity are provided.

1. Molecular DesignMolecular Design
Sbmited by ;Komal rasheedSbmited by ;Komal rasheed
Roll no 3028Roll no 3028
Sbmited to ;sir inam ul haqSbmited to ;sir inam ul haq
Date 29 january2015Date 29 january2015
University of education okaraUniversity of education okara

2. CONTENTSCONTENTS
►IntroductionIntroduction
►Molecular designMolecular design
►Computer aidedComputer aided
►Structures of different moleculeStructures of different molecule
►PrincipalPrincipal
►RefrancesRefrances

3. Medicinal ChemistryMedicinal Chemistry
► Organic ChemistryOrganic Chemistry
► Applied to diseaseApplied to disease
► Example: design newExample: design new
enzyme inhibitor drugsenzyme inhibitor drugs
► doxorubicindoxorubicin
(anti-cancer)(anti-cancer)

4. New Ideas From NatureNew Ideas From Nature
► Natural ProductsNatural Products
ChemistryChemistry
► Chemical EcologyChemical Ecology
 During the next twoDuring the next two
decades: the majordecades: the major
activity in organismalactivity in organismal
biologybiology
► Examples: penicillin,Examples: penicillin,
taxol (anti-cancer)taxol (anti-cancer)

5. Working at the IntersectionWorking at the Intersection
►Structural BiologyStructural Biology
►BiochemistryBiochemistry
►Medicinal ChemistryMedicinal Chemistry
►ToxicologyToxicology
►PharmacologyPharmacology
►Biophysical ChemistryBiophysical Chemistry
►Information TechnologyInformation Technology

6. BindingBinding
► Binding interactionsBinding interactions
are how natureare how nature
controls processes incontrols processes in
living cellsliving cells
► Enzyme-substrateEnzyme-substrate
binding leads tobinding leads to
catalysiscatalysis
► Protein-nucleic acidProtein-nucleic acid
binding controlsbinding controls
protein synthesisprotein synthesis

7. PrinciplesPrinciples
►Structure-Function RelationshipsStructure-Function Relationships
►BindingBinding
 Understand and control binding ->diseaseUnderstand and control binding ->disease
►Molecular RecognitionMolecular Recognition
 How do enzymes recognize and bind the properHow do enzymes recognize and bind the proper
substratessubstrates
►Guest-Host ChemistryGuest-Host Chemistry
 Molecular Recognition in CyclodextrinsMolecular Recognition in Cyclodextrins

8. Molecular RecognitionMolecular Recognition
►Hydrogen bondingHydrogen bonding
•Charge-charge interactions (salt bridges)Charge-charge interactions (salt bridges)
•Dipole-dipoleDipole-dipole
• ππ –– ππ interactions (aromatic)interactions (aromatic)
• Hydrophobic (like dissolves like)Hydrophobic (like dissolves like)
H
δ+
δ−
δ−
δ−
δ−

9. Hosts:Hosts: β−β− cyclodextrincyclodextrin
O
HO
O
OH
OH
O
HO
O
HO
OH
O
HO
O
HO
OH
O
HO
O HO
OH
O HO
O
HO
HO
O
HO
O
OH
HO
O
HO
O
OH
HO

10. Hexasulfo-calix[6]arenesHexasulfo-calix[6]arenes
OH
OH
OH
OH
OH
OH
S
S
S
S
S
S
O
O
O
O
O
O
O
O
O
OO
O
O
O
O
O
O
O

11. Molecular DesignMolecular Design
►Originated in Drug DesignOriginated in Drug Design
►Agricultural, Veterinary, Human HealthAgricultural, Veterinary, Human Health
►Guest - Host ChemistryGuest - Host Chemistry
►Ligands for Inorganic ComplexesLigands for Inorganic Complexes
►Materials ScienceMaterials Science
 Polymer ChemistryPolymer Chemistry
 Supramolecular ChemistrySupramolecular Chemistry
 Semi-conductors, nonlinear phenomenaSemi-conductors, nonlinear phenomena

12. 2D Substructure Searches2D Substructure Searches
► Query:Query:
 Halogen substitutedHalogen substituted
aromatic and a carboxylaromatic and a carboxyl
groupgroup
N
O O
Cl
OO
Cl
NN
N
O O
F
F
O
F
O
O
N
I
O
N

13. Computer AidedComputer Aided
Molecular DesignMolecular Design
Quantitative Structure Activity Relationships-Quantitative Structure Activity Relationships-
QSARQSAR
Quantitative Structure Property Relationships-Quantitative Structure Property Relationships-
QSPRQSPR

14. IntroductionIntroduction
►Uncover important factors in chemicalUncover important factors in chemical
reactivityreactivity
►Based on Hammett Relationships inBased on Hammett Relationships in
Organic ChemistryOrganic Chemistry
►Medicinal ChemistryMedicinal Chemistry
►Guest-Host ChemistryGuest-Host Chemistry
►Environmental ChemistryEnvironmental Chemistry

15. Acetylcholine EsteraseAcetylcholine Esterase
►NeurotransmitterNeurotransmitter
recyclingrecycling
►Design drug that actsDesign drug that acts
like nicotinelike nicotine

16. Acetylcholine EsteraseAcetylcholine Esterase
►RCSB ProteinRCSB Protein
Data Bank (PDB)Data Bank (PDB)
►Human disease-Human disease-
molecular biologymolecular biology
databasesdatabases
 SWISS-PROTSWISS-PROT
 OMIMOMIM
 GenBankGenBank
 MEDLINEMEDLINE

17. Octanol-Water PartitionOctanol-Water Partition
CoefficientsCoefficients
► P =P = C(octanol)C(octanol)
C(water)C(water)
► log Plog P
likelike ∆∆rrG = - RT ln KG = - RT ln Keqeq
► Hydrophobic -Hydrophobic -
hydrophilic characterhydrophilic character
► P increases then moreP increases then more
hydrophobichydrophobic
Octanol
H O2

18. Isonarcotic Activity of Esters, Alcohols,Isonarcotic Activity of Esters, Alcohols,
Ketones, and Ethers with TadpolesKetones, and Ethers with Tadpoles
►log(1/C) = 0.869 log P + 1.242log(1/C) = 0.869 log P + 1.242
►n = 28n = 28 r = 0.965r = 0.965
►subset of alcohols:subset of alcohols:
log(1/C) = 1.49 log P - 0.10 (log P)log(1/C) = 1.49 log P - 0.10 (log P)22
+ 0.50+ 0.50
n = 10n = 10 r = 0.995r = 0.995

19. REFRENCESREFRENCES
►InternetInternet
►www.pakistanmolecularwww.pakistanmolecular design .pptdesign .ppt