Cheminformatics and the Internet - Our Missionacscinf.org/docs/meetings/218nm/presentations/218nm69.pdf · 2013-02-21 · Cheminformatics and the Internet A Subsidiary of Pharmacopeia

Chem informatics and the Internet

A Subsidiary of Pharmacopeia Inc.

Osman F. Güner, Ömer Casher, Ajay V. Shah, Chris Hempill

218th ACS National Meeting, New Orleans LAAugust 22-26, 1999

A Subsidiary of Pharmacopeia Inc

Paradigm Change in the ComputerAge

Computer AccessComputer Access

• Then

• Expert programmers via central mainframes

• Now

• My two kids (ages 9 and 12) via personal computers

(primarily for playing games)

Internet AccessInternet Access

• Then

• Unix guru’s through ARPANET

• Now

• My two kids (ages 9 and 12) via World Wide Web

(primarily for downloading game cheats)


Paradigm Change in ComputationalChemistry

Quantum Chemistry calculationsQuantum Chemistry calculations

• Then

• Theoretical chemists developing new basis-sets, etc.

• Now

• Organic chemists trying to figure out reaction mechanisms,etc.

Molecular Modeling toolsMolecular Modeling tools

• Then

• Computational chemists performing structure-based design,etc.

• Now

• Medicinal chemists prioritizing “drug candidates,” etc.


What Sparked this ParadigmChange?

• E - m a i l , T e l n e t , F T PE - m a i l , T e l n e t , F T P

• Internet t ransport s tandards

• P r o v ided access to centra l inform at ion

• W o rld W i d e W e b - 1993W o r ld W i d e W e b - 1993

• “User- fr iendly” inter face to the Internet v ia aW eb-Brow ser

• Informat ion can be d i s t r ibuted to any m a c h i n ew ith a W eb-server

• H T M L , providing s tandard f i le exchange form at


Impact on Chem istry

• V irtu a l c o m m u n i t i e s o f c h e m is tsV irtu a l c o m m u n i t i e s o f c h e m is ts

• e .g., C h e m C enter , C h e m S o c , C h e m W e b• s e e W arr , W . J.Chem.Inf.C omput.S ci., 1 9 9 81 9 9 8 , 38 , 966-975 .

• Pr im a r y e n try v ia text -b a s e d s e a rch e sPr im a r y e n try v ia text -b a s e d s e a rch e s

• N o n -te x t s e a r c h c o m p o n e n ts n e e d e d t o s u p p o rtN o n -te x t s e a r c h c o m p o n e n ts n e e d e d t o s u p p o rtc h e m istry b e tterc h e m istry b e tter

• e .g. , com p o u n d , spectrum , substructure ,p h a r m a c o p h o r e , sh a p e

• C o rpora te in t ran e ts em e r g e d w i t h b e t t e r s t r u c t u r eC o rpora te in t ran e ts em e r g e d w i t h b e t t e r s t r u c t u r ea n d d e s i g n f o r ch e m istrya n d d e s i g n f o r ch e m istry


Chemistry Related Internet Standards

• Chemical MIME typesChemical MIME types

• see Rzepa, H.S.; Murray-Rust, P.; Whitaker, B., J. Chem. Inf. Comput.Sci. 19981998, 38, 976-982

• Chemical Markup LanguageChemical Markup Language

• http://www.xml-cml.org/

• VRMLVRML

• See Casher, O.; Page, C.; Rzepa, H. Chem. Brit., 19881988, 34(9), 26-30.

• See Dolata, D.P.; Wathen, S.P. J. Mol. Graph. Model. 19981998, 16, 37-46.


Web-Enabled 3D “Free” ChemicalVisualizers

• RasMol RasMol - Roger - Roger SayleSayle

• http://www.umass.edu/microbio/rasmol/

• ISIS/Draw - MDLISIS/Draw - MDL

• http://www.mdli.com/download/idraw.html

• WebLab Viewer - MSIWebLab Viewer - MSI

• http://www.msi.com/download/viewer/lite/


Various Web-basedChem informatics Software• C h e m F i n d e rC h e m F i n d e r, (, (C a m b r i d g S o f tC a m b r i d g S o f t))

• index chem ical in form a t i o n

• C h e m S y m p h o n yC h e m S y m p h o n y

• J a v a p a c k a g e , s e e B r e c h e r Chimia, 1 9 9 81 9 9 8 , 52 (11) , 668-672

• S p o tf i r eS p o tf i r e D i s c o v e r y S e rver D i s c o v e r y S e rver

• n a v igat ional a id for databases

• M i n e S e tM i n e S e t

• 3 D v isu a l navigat ion

• E y e C h e mE y e C h e m

• v isu a lizat ion toolkit , s e e C a s h e r J.M ol.Graph., 1 9 9 41 9 9 4 ,1 2 (3) , 226-230


Research Over the Internet

• D ata access - e .g., p r o t e i n m ass spec t raD ata access - e .g., p r o t e i n m ass spec t ra

• F e n y o et al . , A n al.Chem., 1 9 9 61 9 9 6 , 68 (23) ,721A

• D ata an a l y s i s - e .g. , scan n i n g p rob e m i c r o s c o p yD ata an a l y s i s - e .g. , scan n i n g p rob e m i c r o s c o p yd a ta an a l y s i s s y s t e md a ta an a l y s i s s y s t e m

• h t tp ://pharm 6.p h a r m .not t ingham .ac.u k /process ing/m ain.htm l

• I n s tru m e n t operat ion - e .g . , rem o te con tro l o fI n s tru m e n t operat ion - e .g . , rem o te con tro l o fN M R s y s t e m sN M R s y s t e m s

• B u s z k o et al . , A ppl.M ag.R eson., 1 9 9 71 9 9 7 , 12 (95) ,101

• S i m u l a t i o n o f s p e c t r a - e .g. , IR spec t ra s im u l a t i o nS i m u l a t i o n o f s p e c t r a - e .g. , IR spec t ra s im u l a t i o na n d p r o c e s s i n ga n d p r o c e s s i n g

• h ttp://w w w 2.ccc .u n i-er langen .de/research/ir/ engl ish


Examples for Web-Access toChem ical Information

• E P A r u l e s a n d r e g u l a t i o n sE P A r u l e s a n d r e g u l a t i o n s

• h ttp://w w w .e p a .g o v / e p a h o m e/rules .htm l

• D atab a s e o f G - p r o t e i n c o u p l e d r e c e p t o r sD atab a s e o f G - p r o t e i n c o u p l e d r e c e p t o r s

• h ttp://w w w -g r a p .fragm e d .u it. n o / G R A P / h o m epage .htm l

• D atab a s e o f p rote in s t ruc turesD atab a s e o f p rote in s t ruc tures

• h ttp://p d b .p d b .b n l.g o v

• D atab a s e o f n u c l e i c a c i d sD atab a s e o f n u c l e i c a c i d s

• h ttp://n d b s e r v e r .rutgers .e d u

• B i o c h e m ica l com p o u n d s d a tab a s eB i o c h e m ica l com p o u n d s d a tab a s e

• h ttp://w w w .ibc.w u stl.e d u / k lotho/ #c o m p o u n d s


Chemistry Education Through theInternet

• List of chemistry courses and tutorialsList of chemistry courses and tutorials

• http://www-rohan.sdsu.edu/staff/drjackm/chemistry/chemlink/teach/teach1.html

• http://www.utexas.edu/world/lecture/ch

• P-P-ChemChem course at University of Delaware course at University of Delaware

• Noggle and Dybowski, J.Chem.Edu., 19981998, 75(11), 1499.

• Drug Design chemistry course at University of NebraskaDrug Design chemistry course at University of Nebraska

• Liu et al., J.Chem.Edu., 19981998, 75(1), 123-125.


Chemistry Education Through theInternet

• Web-based drug design courseWeb-based drug design course

• http://www.netsci.org/Courseware

• Many examples of Web-based chemistry coursework (HenryMany examples of Web-based chemistry coursework (HenryRzepaRzepa Home Page) Home Page)

• http://www.ch.ic.ac.uk/rzepa

• Degree courses over the Internet: Structure-Based Drug DesignDegree courses over the Internet: Structure-Based Drug Designat University of at University of NottinghamNottingham

• Burt, C. et al., ACS 217th National Meeting, Anaheim 1999, CINF-68.


Recent Reviews of Chemistry onInternet

• Heller, S. R. “Chemistry on the Internet: the Road to Everywhere andNowhere,” J. Chem. Inf. Comput. Sci., 19961996, 36, 205-213.

• Boyd, D. B. “Compendium of Software and Internet Tools for ComputationalChemistry,” Rev. Comput. Chem. 19971997, 11, 373-399.

• Wiggins, G. “Chemistry on the Internet: The Library on your Computer,” J.Chem. Inf. Comput. Sci., 19981998, 38, 956-965.

• Güner, O.F. and Casher O. “Role of the Internet in Cheminformatics,” Curr.Opin. Drug Disc. & Dev., 19991999, 2(3), 204-208.


Some Examples for CommercialIntranet Informatics Software

• MedChem and Diversity Explorer - MSIMedChem and Diversity Explorer - MSI

• ChemScape ChemScape Chime - MDLChime - MDL

• ChemEnlighten ChemEnlighten - - TriposTripos

• Interactive Labs - ACD/LabsInteractive Labs - ACD/Labs


W ebL ab M edChem Explorer

U t i l i z e s t h e e x i s t i n g i n tran e t in f rastru c ture a t yourU t i l i z e s t h e e x i s t i n g i n tran e t in f rastru c ture a t yourc o m p a n yc o m p a n y

M a n a g e s t h e p r o j e c t s a n d e x p e r i m e n ts v ia W e bM a n a g e s t h e p r o j e c t s a n d e x p e r i m e n ts v ia W e bb row s e rsb row s e rs

C l i e n t -server W e b e n v i ron m e n t to g e t h e r w i t h aC l i e n t -server W e b e n v i ron m e n t to g e t h e r w i t h an a t i v e a p p l i c a t i o n f o r th e b e s t d is t r ib u t i o n o fn a t i v e a p p l i c a t i o n f o r th e b e s t d is t r ib u t i o n o fr e s o u r c e sr e s o u r c e s

I n tegra tes w ith y o u r ex is t in g i n f o r m a t i c sI n tegra tes w ith y o u r ex is t in g i n f o r m a t i c se n v i r o n m e n t to p r o v i d e a d d e d v a l u e t h r o u g he n v i r o n m e n t to p r o v i d e a d d e d v a l u e t h r o u g hm o d e l i n g a n d a n a l y s i s t o o l sm o d e l i n g a n d a n a l y s i s t o o l s


W ebL ab Environment

MSIMethods

CORPORATEINTRANET

THE INTERNET

Browser

InformationServer (documentation/references/publications)

Database

Broker

Methods Manager

non-MSIMethod

Broker


M edChem Explorer A pplications

I n 1 9 9 8 - W e b L a b 1 . 5I n 1 9 9 8 - W e b L a b 1 . 5

[re l e a s e d ][re l e a s e d ]

• D a t a b a s e A c c e s s

• C o n form ers

• Proper ty Ca lcu la tor

• A lig n / P h a r m a c o p h o r e

I n 1 9 9 9 - W e b L a b 1 . 6I n 1 9 9 9 - W e b L a b 1 . 6

[to b e r e l e a s e d ][to b e r e l e a s e d ]

• M o lecular O v e r l a y

• A ct iv i ty Predic t ion


M edChem Explorer DB A ccessD irec t access to th i rd-par ty da tab a s e sD irec t access to th i rd-par ty da tab a s e s

• ISIS®

• C a talyst ®

• D a y light

R ich S earch O p t ion sR ich S earch O p t ion s

• Text -based ( IS IS , C a talyst)

• 2 D S imilar i ty ( ISIS , D a y lig h t)

• 2 D S u b s tructure ( ISIS , D a y lig h t, C a talyst)

• 3 D P h a r macophore ( IS IS , Cata lys t )

• 3 D S h a p e (Catalyst )

T a b u l a t e d r e s u l t sT a b u l a t e d r e s u l t s

• o p t ion to present resul ts in M S E x c e l

• o p t ion to expor t S D F ile






M edChem Explorer Conformers

E n e r g y m i n i m i z a t i o nE n e r g y m i n i m i z a t i o n

• o p t ions for se t t ing defaul t for us ing di f ferentforcef ie lds (D re id ing a n d C F F 9 7 )

C o n f o r m a t i o n g e n e r a t i o nC o n f o r m a t i o n g e n e r a t i o n

• Sys tem a t ic conform a tio n a n a lysis

• low e s t e n e r g y c o n f o r m a t ions

• d iverse se t o f conform at ions

• D iverse sam p lin g o f conform at ional space



• o p t ion to expor t S D F iles


Conformations Overlaid


M edChem Explorer PropertyCalculator

C a l c u l a t e h u n d r e d s o f p r o p e r t i e s /d e s c r i p t o r sC a l c u l a t e h u n d r e d s o f p r o p e r t i e s /d e s c r i p t o r s

• C o n form at ional

• c o n f. en e r g y p e n a l t y , lo w e s t e n e r g y , etc.

• E lectronic

• d ipole m o m e n t, su m o f ch a r g e s , etc.

• Structura l

• M W , No. o f H b o n d donors/acceptors , e tc .

• T h e r m o d y n a m ic

• l o g P , molar re fract iv i ty , heat of form ation, etc .

• Spat ia l

• area , m o lecular vo lum e, PM I, etc.

• Q u a n t u m M echanica l (M O P A C )

• H O M O , L U M O , heat of form a tion, etc .

C a l c u l a t e C a l c u l a t e L i p i n s k i L i p i n s k i p r o p e r t i e sp r o p e r t i e s



M edChem ExplorerA lign/Pharmacophore

M o l e c u l a r a l i g n m e n t b a s e d o n c o m m o n c h e m i c a l f e a t u r e sM o l e c u l a r a l i g n m e n t b a s e d o n c o m m o n c h e m i c a l f e a t u r e s

• H b o n d a c c e p t o r / d o n o r

• L ipophi l i c

• Negat ive or pos i t ive ionizable

D e v e l o p m e n t o f p h a r m a c o p h o re m o d e l s b a s e d o nD e v e l o p m e n t o f p h a r m a c o p h o re m o d e l s b a s e d o na l i g n m e n ta l i g n m e n t

• p h a r m a c o p h o r e m o d e l s c a n b e u s e d t o s e a r c hcata lys t databases v ia M E .D B A ccess



• e x p o r t s a l i g n e d h i t s a n d / o r p h a r m a c o p h o r e s


A Pharmacophore M odel


W ebL ab 1.6

T o b e r e l e a s e d i n 1 9 9 9T o b e r e l e a s e d i n 1 9 9 9

T w o n e w a p p l i c a t ion s :T w o n e w a p p l i c a t ion s :

• M olecular O v e r l a y

• A ctivity P r e d ictio n

E n h a n c e m e n ts to E n h a n c e m e n ts to D B A c c e s sD B A c c e s s

• Proper ty search w ith D a y lig h t databases

M e d C h e m a n d D ivers i ty Explorer ge t t in g c loserM e d C h e m a n d D ivers i ty Explorer ge t t in g c loser

I m p r o v e d s t a b i l i tyI m p r o v e d s t a b i l i ty


Acknowledgements

O m er C a s h e rO m er C a s h e r

C h r is C h r is H e m p i l lH e m p i l l

A j a y S h a hA j a y S h a h

Cheminformatics and the Internet - Our Missionacscinf.org/docs/meetings/218nm/presentations/218nm69.pdf · 2013-02-21 · Cheminformatics and the Internet A Subsidiary of Pharmacopeia

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