Project Design

Rama K. Mishra

**** *. ******** **., **** #*

Chicago, IL 60607

Home: 312-***-****

Cell: 312-***-****

E-mail: ************@*****.***

SUMMARY

Working as a Computational Chemist for more than 8 years in a Bio-Pharmaceutical

company. Primary expertise is in the areas of Ligand based and Structure based drug

design with proven success stories.

STRENGTHS

Adept at developing novel ways to implement and integrate computational tools;

practical knowledge of both drug development and discovery; experience in ligand based,

structure based, statistical based, simulation and ab-initio, DFT based modeling

techniques and working with a wide variety of computational chemistry software such as

TRIPOS,ACCELRYS,SCHRODINGER,MOE,4D-QSAR,MI-QSAR, Gaussian, MOPAC

and AMPAC.

Professional Experience

deCODE CHEMISTRY, Woodridge, IL (9/2001 – present)

Senior Research Scientist – Computational Chemist

Responsible for development of computational bio-pharmaceutics tools and strategy for

integration of computational / modeling tools to standard research protocols.

• Leading role in development of strategy and implementation of computational

tools initiating from the Homology Model of a Kinase, novel leads obtained

using Phamacophore Models derived from Structure Based Focusing (SBF) and

the Composition pattern patented without any Medicinal/Synthetic Chemistry

efforts.

US Patent: US 200*-*******

• A ligand based designed performed for a GPCR target with the Pharmacophore

Models, ComFA / ComSIA and EVA techniques. The project went from hit 2

lead and the compound is in the clinic. (Gene to Drug). DGO41 an anti-platelet

compound developed for the prevention of arterial thrombosis.

Compound (DGO41) in the phase II Clinical Trial Completed

• Project leader of Computational tools development group for a Structure based

Drug Design program (Myocardial Infraction Project). Developed a novel QSAR

technique to rapidly predict the IC50/Binding Energy of the Ligands with a very

high predicting ability. In-silico designed compounds finally synthesized and

now in clinical trial. DGO51 targeting the leukotriene pathway for the prevention

of heart attack.

Compound (DGO51) phase II Clinical Trial Completed,

US Patent 7,402,684

• Computational Project leader in the neurodegeneration (PDE4) project where the

identified candidate was approved by the FDA to enter clinical trials (CNS).

DG071 and a platform for other PDE4 modulators with therapeutic applications

in Alzheimer's disease and other conditions

Compound DGO71 Pre-clinical trial

• Computational leader in a successful Fragment of Life (FOLTM ) Library design

with the Crystallographic Group. Till today, the in-silico screening of FOL

followed by crystallographic screening have resulted fragments hits across 17

different targets such as Kinases, NS3 Helicase, Hydrolase, and the Infectious

diseases targets BUPS.

• Imparts training to Medicinal Chemists and Biologists to implement the

Benchware Docking tools in an Oracle data base platform and ISIS db to

maintain the user database.

• Evaluated commercial computational bio-pharmaceutics software

• Maintain the Company proprietary Compound database (~ 2 million compounds)

• Generated the low energetic conformational CATALYST data base (1.2 million

compounds) for in-silico screening

• Designed many algorithms and written Scripts in Sybyl /Python Programming

Languages for customization

University of Illinois at Chicago (College of Pharmacy), IL (05/2000 – 09/2001)

Senior Research Associate

• Lead Program designer for the 2D molecular similarity analysis part of 4D-QSAR

program (4D-QSAR Similarity software commercially available)

• Developed a versatile technique for the alignment of molecules for the

implementation of 4D-QSAR

• Co-developer of Membrane – Interaction QSAR (MI-QSAR) for ADME/Tox

properties (MI-QSAR software commercially available)

• Supervise the graduate students

University of Valencia (Department of Pharmacy) SPAIN (12/1999 – 05/2000)

Visiting Research Scientist

• Developed and implemented the unique role of -XH (X=O,N,S) vibrational

frequency in Antibiotics with discriminant function analysis

• Impart teaching on the role of Quantum Chemistry in Drug Discovery to graduate

students

• Active member Molecular Connectivity and Drug Discovery Research Unit,

University of Valencia, Valencia, Spain

National Cheng-Chung University (Dept of Chemistry & Biochemistry) Chai-Yi,

Taiwan (05/98 – 12/99)

Visiting Research Scientist

• Leader in developing the ab-initio and DFT methods to handle the molecules of

Biologically importance

• Developed and implemented the high level Quantum Chemical techniques to

study the Hydrogen Bonding in Nucleic Acid Base Pair: Cytosine Dimer

• Developed novel Quantum Chemical Methods to hypothesize and prove the

Fullerene Growth Mechanism

• Supervise the graduate students

Research Interest and Expertise:

•2D, 3D, 4D - QSAR Analysis

• Ligand Docking and Scoring (Structure Based Design)

• Active Analog Approach (Ligand Based Design)

• Library Design (VHTS)

• Lead Identification

• Lead Optimization

• Homology Modeling

•Molecular Dynamics Simulation

•Molecular Similarity / Diversity Analysis

•Partial Least Squares and Chemometrics

• Alignment Analysis

•Genetic Algorithm Optimization

•Quantum Chemistry: ab-initio and DFT

•Molecular Graph Theoretical Approach to Medicinal Chemistry

• ADME/TOX Property Predictions

Software Expertise

Accelrys:

1) Cerius 2 Environment all Modules

2) Catalyst

3) InsightII

4) Discovery Studio

Tripos:

1) Sybyl

2) DISCO and DISCOTech

3) Distill

4) SURFLEX/FlexX/FlexS/FlexE/Flexidock

5) CoMFA/ CoMSIA/ EVA/Topomer CoMFA

6) Benchware dock ( LITHIUM)

SCHRODINGER

GLIDE, JAGUAR, LIASON, Q-SITE, PRIME, QUICK-PROP, PHASE, STRIKE

MOE

PHARMACOPHORE DISCOVERY, HTS-QSAR, BREED, STRUCTURE

ACTIVITY REPORT etc.

4D-QSAR Analysis and Its Molecular Similarity Module

(Membrane Interaction) MI-QSAR analysis for ADME property estimation

Programming Languages

Sybyl, Fortran, C, C++, JAVA, Python, HTML, SQL,SAS

a) Networking: Unix/Linux and Windows NT

b) Operating Systems: Windows, Unix, Linux

c) Statistical Packages: SAS, SPSS, WOLF (GFA), BMDP

ACADEMIC HISTORY

PhD: Physical Chemistry Sambalpur University, India

M.Sc: Chemical Physics & Physical Chemistry, Sambalpur University

Published Articles (1995-current)

1 Antagonists of the EP3 Receptor for Prostaglandin E2 Are Novel Antiplatelet Agents

That Do Not Prolong Bleeding

J.Singh, W.Zeller, N.Zhou, G.Hategen, R.Mishra, A.Polozov, P.Yu, E.Onua,

J.Zhang, D.Zembower, A.Kiselyov, J.Ramirez, G.Sigthorsson,

J.Bjornsson, M.Thorsteinsdottir, T.Andresson, M.Bjarnadottir,

O.Magnusson, J.Fabre, K.Stefansson and M.Gurney

ACS Chem. Biol., 2009, 4 (2), pp 115–126

2 Peri-substituted hexahydro-indolones as novel, potent and selective human

EP3 receptor antagonists

M.O’Connell, W.Zeller, J.Burgeson, R.Mishra, J.Ramirez, A.Kiselyov

M.E Gurney, J.Singh

Bioorganic & Medicinal Chemistry Letters, 19(3), 2009, 778-782

3 Discovery of Leukotriene A4 Hydrolase Inhibitors Using Metabolomics Biased

Fragment Crystallography

Douglas R. Davies, Bjorn Mamat, Olafur T. Magnusson, Jeff Christensen, Magnus

H. Haraldsson, Rama Mishra, Brian Pease, Erik Hansen, Jasbir Singh, David

Zembower, Hidong Kim, Alex S. Kiselyov, Alex B. Burgin, Mark E. Gurney and

Lance J. Stewart

J. Med. Chem., 2009, 52 (15), pp 4694–4715

4 DcpS as a Therapeutic Target for Spinal Muscular Atrophy

Jasbir Singh, Michael Salcius, Shin-Wu Liu, Bart L. Staker, Rama Mishra,

John Thurmond, Gregory Michaud, Dawn R. Mattoon, John Printen, Jeffery

Christensen, Jon Mar Bjornsson, Brian A. Pollok, Megerditch Kiledjian, Lance

Stewart, Jill Jarecki and Mark E. Gurney

ACS Chem. Biol., 2008, 3 (11), pp 711–722

5 Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives

as SMN2 promoter activators for the potential treatment of spinal muscular atrophy

John Thurmond, Matthew E. R. Butchbach, Marty Palomo, Brian Pease,

Munagala Rao, Louis Bedell, Monica Keyvan,Grace Pai, Rama Mishra,

Magnus Haraldsson, Thorkell Andresson, Gisli Bragason,Margret

Thosteinsdottir Jon Mar Bjornsson, Daniel D. Coovert, Arthur H. M. Burghes,

Mark E. Gurney,and Jasbir Singh

J.Med.Chem 51(3), 2008, 449-69

6 A Density Functional Theory Study for the Hydrogen-Bonded Nucleic Acid

Base

Pair: Cytosine Dimer

Prabhat K. Shoo, Rama K.Mishra, S.L.Lee

J. Phys. Chem. A, 109 (12), 2005, 2887 –2893

7 Predicting Blood-Brain Barrier partitioning of Organic Molecules using

Membrane Interaction QSAR (MI-QSAR) Analysis

M.Iyer, Rama K.Mishra,A.J.Hopfinger;

Pharmaceutical Research, 19(11), 1611- 1621, 2002

8. Free Energy force Field (FEFF) 3D-QSAR Analysis of a Set of

Plasmodium falciparum Dihydrofolate Reductase inhibitors.

Oslado S, Rama K.Mishra, A,J.Hopfinger

J.Computer-Aided Molecular Design 13(46),1-24,2001

9. The Use of Hasse Diagrams as a potential approach for Inverse QSAR.

Rama K.Mishra, R.Briggeman etal. ;

SAR -QSAR and Environ.Res. 11,2001, 473-487

10 Getting discriminant functions of antibacterial activity from physico –

chemical and toological parameters.

Rama K.Mishra and J.Galvez

J.Chem.Inf. and Comput. Sci 41, 2001, 387-393

11 Computaional studies of the Growth Mechanism of Small Fullerenes : A

Ring-Staking Model

Rama K.Mishra, S.L.Lee etal.;

J. Chinese Chemical Society,50,2003,575-582

12 A Nonlinear Optical Study of some Antibacterials : A Structure Optical

Property Relationship (SOPR) study.

Rama K. Mishra and J.Galvez; Int. J.Quantum. Chem. 2003

13. Growth Mechanism of C28(D2) fullerene : Energetics and Transition

State structure analysis.

Rama K.Mishra, Y-T.Lin,S.L.Lee Int.J.Quantum.Chem, 84,642-648,2001

14. Theoretical Studies of Fullerene Growth Mechanism : Ring – Collapse and

Cascade bond formation .

Rama K.Mishra,Y-T.Lin, S.L.Lee; J. Chem. Phys . 112(14),2000,6355-6364

15. Quantum Chemical AM1 study of Growth Mechanism of Fullerenes : A

Facile C2 Insertion Technique .

Rama K.Mishra, Y-T.Lin,S.L.Lee;J. Phy. Chem (B), 103(16),1999,3151-3155

16 Capping C72 through C6 : studying the relative stability of the five C78

Fullerene Isomers.

Rama K.Mishra,Y-T Lin, S-L.Lee; Chem.Phy. Lett. 302,1999,108-112

17. Growth Mechanism of C28(Td) fullerene : Energetics and Transition

State structure analysis.

Rama K.Mishra, Y-T.Lin,S.L.Lee; Chem.Phys. Lett. 313, 1999,437

18. A Comparative study of static third-order polarizabilities of Bowl / Non

Cages to Cage structures .

Rama K.Mishra, Y-T.Lin, S.L.Lee Mol. Phys. 97(8),1999, 987

19. A nonlinear optical study of the five IPR isomers of C78 generated

through Capping C72 through C6 .

Rama K.Mishra, Y-T.Lin,S-L Lee; Int. J. Quantum. Chem. 77, 2000, 574-579

20. A study of (2Pi+4Pi) chemical reactions through Edge-Loop /Loop-Edge

Conversion techniques.

Rama K.Mishra, S.L.Lee; Int. J. Quantum. Chem . 75(4/5),1999,821

21. Numerical determination of the Kekule Structure count of some

symmetrical PAHs and their relationship with pi-electronic energy.

Rama K.Mishra,S.M.Patra ; J.Chem. Inf. Comput. Sci. 38,1998,113-121

22. On the pairing of the Molecular Orbitals energy levels of Heteroconjugated

molecules.

Rama K.Mishra, S.M.Patra and I.Gutman;J.Serb.Chem.Soc. 63,1998, 25

23. A divide and conquer algorithm use to study some Benzenoid

Hydrocarbons. A Graph Theoretical and Computational Approach.

Rama K.Mishra and S.M.Patra ;Bull. Chem. Soc.(Jpn) 71,1998,1013

24. Quantum chemical AM1 treatment of the Circumscribing Algorithm :

Fullerene Growth Mechanism .

Rama K.Mishra, Y-T.Lin,S.L.Lee; J.Chem. Inf. Comput. Sci. 39,1999, 1090

25. A Graph Theoretic Study of certain Interstellar Reactions.

Rama K.Mishra, S.M.Patra, B.K.Mishra ;Int. J. Quantum. Chem.

62,1997,495

26. Influence of the Huckel K parameters on the pairing of the eigenvalues of

Heteroconjugated molecules.

Rama K.Mishra and S.M.Patra;J.Chem. Inf. Comput. Sci .37,1997,495

27. Ordering the Isomeric molecules through the graph spectrum . Generation of

Two topological indices depicting the branch and linear characters ;

Rama K.Mishra and S.M.Patra Bull.Chem.Soc(JPN). 70,1997,997

28. Optimal parameterization of structure for predicting the properties of

Alkanes. A Quantitative Structure Property Relationship (QSPR).

Rama K.Mishra, M.Kunwar and B.K.Mishra

Ind. J.Chem. (A) 35A,1996,1026

29. A Novel use of the Huckel parameters for pairing the eigenvalues in graph

spectrum.

Rama K.Mishra, S.M.Patra, B.K.Mishra Ind. J.Chem (A) 35A,

1996,813.

30. Splitting of the characteristic polynomials using a computational technique to

obtain the Mirror plane, Two-,Three- and n-fold symmetric graphs.

Rama K.Mishra and S.M.Patra Int. J. Quantum. Chem. 53,1995, 361

31. Factors of polyhedral spectra : A computational approach

Rama K.Mishra and S.M.Patra J.Mol.Struct.(THEOCHEM) 342,1995,201

32. Ordering the Topological Indices through Principal Component Analysis .

Rama K.Mishra J. Math. Chem. (Sp. Issue) 1995,131

33. A QL program in FORTRAN code (SUP. 26526) 1995. The British Lending

Library, Document supply Center, England.

34. On the HOMO-LUMO separation in graph spectrum of heterocyclobutadienes.

Rama K.Mishra and S.M.Patra;Ind. J.Chem. 29A,1995,370

35. A fractral study of aliphatic compounds : A Quantitative Structure

Property Correlation (QSPC) study through the topological parameters

and bulk properties.

Rama K.Mishra B.K.Mishra ; Ind. J.Chem . 28A, 1995,927

36.

Papers Communicated / under preparation

1. A Three Dimensional Phamacophore Model for EP3 Antagonists

(Communicated to J.Med.Chem –2009)

2. Alignment versus non-alignment techniques used in 3D QSAR Models for the

EP3 antagonists.

Under Preparation

3. A structure activity relationship of LTA4H receptor : A structure based drug

Design

Under Preparation

REFERENCES

1. Alex Kiselyov, Ph.D

President deCODE Chemistry

2501 Davey Road, Woodridge, IL 60517

Office: 630-***-****

*********@******.***

2. Prof . A.J. Hopfiger

Professor and Director Molecular Modeling

College of Pharmacy,

University of New Mexico,

Albuquerque, New Mexico 87131

*********@***.***

3. Jasbir Singh, Ph.D

Vice President Medicinal Chemistry

2501 Davey Road,

deCODE Chemistry,

Woodridge, Il 60517

******@******.***

Ph# 630-***-****

4. David A. Eiznhamer, Ph.D

Executive Vice President (Clinical Development)

Advanced Life Sciences

1400 Davey Road, Woodridge, IL 60517

Office: 630-***-****

**********@********************.***

Contact this candidate