Design Engineering

F. RAYMOND SALEMME, PH.D

F. Raymond Salemme, PhD

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

www.thermofluor.org

Engineered Nanostructure

SUMMARY

Seasoned entrepreneur with proven ability to recruit, organize and direct multidisciplinary scientific

teams, build effective business strategies, and commercialize innovative, high-value technology.

Experienced fund raiser, including generation of Federal funding for basic research, start-up venture

capital financing, and access to public markets through both conventional IPO and reverse merger

strategies.

Expertise in intellectual property development. Inventor on 34 issued US patents.

Broad scientific and technology expertise, as demonstrated by successful academic career, pioneering

publications in scientific journals, innovative patents, and extensive private and public sector advisory

work.

Expertise in drug discovery technology including biochemistry, structure-based drug design,

cheminformatics, modeling and simulation technology, combinatorial and medicinal chemistry, high-

throughput screening, biophysics and functional genomics.

Expertise in basic science and advanced technology for nanotechnology including molecular design,

property simulation, synthesis, fabrication, and property measurement of advanced polymers and

protein-based molecular devices.

PROFESSIONAL EXPERIENCE

Imiplex LLC Bristol, PA

Founder & President 4/03 - Present

www.imiplex.com ***@*******.***

Imiplex is a nanotechnology company using protein engineering to design, produce, and commercialize

modular components for applications including biosensors, biomaterials, and targeted diagnostics and

therapeutics.

Imiplex focuses on the development modular components that allow the flexible, controlled assembly

of nanostructures using a combination of top-down and bottom-up assembly strategies.

Imiplex has developed proprietary computer codes for engineering nanostructures and filed an

extensive intellectual property portfolio covering engineered protein compositions and nanostructure

applications.

Imiplex was founded by Ray Salemme and Patricia Weber, PhD, scientists responsible for the

structural elucidation of streptavidin, a basic component of the Imiplex s modular assembly

technology platform.

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F. R. Salemme, PhD Resume

VIA Sciences Board of Directors (www.viascience.com) 6/04 - Present

VIA Science s REFS platform is used for analysis of big data structures, with initial applications in

drug discovery, patient stratification for clinical trials, and patient outcomes evaluation.

ExSAR Board of Directors (www.exsar.com) 6/09 - Present

ExSAR offers contract Mass Spectroscopy HD Exchange services for protein structural analysis,

including epitope mapping and biosimilars characterization.

Aria Neurosciences Board of Directors (www.arianeurosciences.com) 3/12 - Present

Aria Neurosciences is a company engaged in the development of CNS drugs.

IonField Systems Board of Directors (www.ionfieldsystems.com) 7/12 - Present

IonField Systems is a company that develops and markets instrumentation for drug screening and

high-throughput diagnostic applications.

Redpoint Bio Corporation Ewing, NJ

Chief Executive Officer & Board of Directors 6/04 - 9/11

Redpoint Bio was a biotechnology company involved in the discovery of natural taste enhancers allowing

the use of reduced quantities of sugar and salt in food and beverage applications.

Recruited as CEO in June 2004 at close of Series A venture financing to develop Redpoint technical

and strategic plan.

Developed a discovery platform incorporating both modern drug discovery and cheminformatics

technology, as well as novel operant animal models for tastant discovery.

Discovered RP44 (Reb C), a novel all-natural sweetness enhancer derived from stevia, subsequently

affirmed GRAS and licensed to IFF for commercialization.

Took Redpoint public through a reverse-merger PIPE transaction in 2007, raising $33 Million in gross

proceeds.

Forged collaborations with Givaudan, the number one flavor and fragrance company worldwide, and

Coca-Cola, the number one beverage company worldwide.

3-Dimensional Pharmaceuticals, Inc. Exton, PA

President & Chief Scientific Officer 6/96-4/03

President & Chief Executive Officer 2/93-6/96

Scientific founder, director, and executive officer of 3-Dimensional Pharmaceuticals. Inc. [3DP]. 3DP was

a Nasdaq-listed pharmaceutical company developing drugs for cardiovascular disease and cancer, and

had grown to over 200 employees when it was acquired by Johnson & Johnson in April 2003. 3DP

developed DiscoverWorks, a proprietary chemi-informatic technology that integrates structural biology,

combinatorial chemistry, and high throughput screening for cost-effective pharmaceutical discovery in the

post-genomics era. As founder and executive officer of the company I achieved the following objectives:

Developed 3DP business plans for venture funding, raising over $40 million in equity backed capital.

Developed road show raising $85 million, valuing 3DP at ~$335 million at its August 2000 IPO.

Developed and implemented 3DP s R&D plan for novel small molecule pharmaceuticals for

cardiovascular disease and cancer. Outlicensed lead cardiovascular programs to Wyeth and Johnson

& Johnson at completion of Phase I clinical development.

Developed and commercialized ThermoFluor HTS software and instrumentation for label-free drug

screening and related applications requiring thermodynamic measurements of protein stability.

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F. R. Salemme, PhD Resume

3-Dimensional Pharmaceuticals, Inc. [Continued]

Developed and implemented DiscoverWorks strategy, using 3DP s high-throughput drug discovery

platform to generate revenue that 3DP reinvested to finance internal drug discovery programs.

Developed collaborations and licensing agreements with Bristol-Myers Squibb, Merck KGaA, Boeringer

Inglelheim, Heska, BioCryst, Aventis Crop Science, Merck and other companies, raising ~$40 million

in cash and operating revenue.

Co-Invented DirectedDiversity control technology for combinatorial chemistry and ThermoFluor

high throughput drug screening technology, key components of 3DP s DiscoverWorks platform.

Developed 3DP intellectual property licensing strategy, generating multi-million dollar revenues.

Built and directed industry-leading scientific teams in molecular biology, biophysics, combinatorial

chemistry, medicinal chemistry, structural biology, and advanced computer technology for chemi-

informatics. Recruited world-class Scientific Advisory Board for 3DP.

Generated over $3 million in NIH SBIR and NIST ATP Federal research support to fund early 3DP

technology development.

Sterling Winthrop Pharmaceuticals Collegeville, PA

Senior Director 3/91-2/93

Biophysics and Computational

Chemistry

Established and directed the Department of Biophysics and Computational Chemistry that consolidated

company-wide technical resources for structure-based drug discovery and rational drug design.

Recruited scientific teams and integrated biophysical methods of structure determination (including

protein x-ray crystallography, high-field NMR, and optical spectroscopy) with the development and

use of Computer-Aided Design tools for rational drug design and protein engineering.

Integrated scientific teams over three Sterling Winthrop operating sites; developed and implemented

consolidation plan at Collegeville site.

Directed structure-based drug design programs for matrix metalloproteases, elastase, and

interleukin-converting enzyme, leading to preclinical candidates within 2 years from program

initiation.

Directed collaborative research program with Sandia Laboratories for the application of advanced

computational methods for drug discovery.

DuPont Merck Pharmaceuticals Inc. Wilmington, DE

Research Leader 1/91-3/91

Protein Structure & Drug Design

Life Sciences components of DuPont Central Research were merged into the DuPont Merck

Pharmaceuticals joint venture in 1991. At DuPont-Merck Pharmaceuticals I directed a group of

experimental biophysicists and computational chemists focused on the rational design of new

pharmaceuticals, including a novel class of symmetric uriedo-based HIV protease inhibitors, and several

boronic acid derivatives of DUP 714, a direct thrombin inhibitor for cardiovascular disease.

July 18, 2012 Page 3 of 13

F. R. Salemme, PhD Resume

DuPont Company Wilmington, DE

Research Leader 1985-1990

Central Research and Development

At DuPont CR&D, I built and supervised a multidisciplinary scientific group that included biophysicists,

crystallographers, computational chemists, and applied mathematicians. This group collaborated with

molecular biologists, biochemists, and synthetic chemists in CR&D and in DuPont Operating Departments

on basic and applied problems in structural analysis, molecular modeling, and simulation.

Supervised X-ray structure determination of proteins of pharmaceutical interest including streptavidin,

protocatechuate dioxygenase, retroviral proteases, interleukin 1, and phospholipase A2 to support

efforts in Dupont Pharmaceuticals and Diagnostic Products operating divisions.

Supervised structure-based design of new drugs for viral proteases and phospholipase and modified

chromophoric ligands for streptavidin.

Developed new computational simulations of protein electron transfer reactions, biopolymer elasticity,

and dynamics of phospholipid micelles.

Developed real-time x-ray process monitoring instrumentation for carbon fiber production.

Developed new computational modeling tools for simulation of periodic 3D polymer lattices.

Developed and commercialized the first robotic system for protein crystallization.

Team leader for engineered biopolymers with advanced material applications.

Genex Corporation Gaithersburg, MD

Director 1983-1984

Protein Engineering Department

At Genex, I recruited and technically supervised one of the first integrated research teams in the

biotechnology industry to successfully engineer proteins using a combination of X-ray structural studies

and computer-aided design methods.

Developed pioneering technology for rapid protein structure determination using 2-dimensional X-ray

area detectors.

Designed and engineered the first single-chain Fv antibodies for diagnostic and therapeutic

applications.

Developed advanced computer programs for protein engineering to produce improved catalysts with

properties suitable for industrial process environments.

ACADEMIC CAREER

University of Arizona Tucson, AZ

Professor of Biochemistry 1982-1983

Associate Professor of Biochemistry 1978-1982

Assistant Professor of Chemistry 1973-1978

Pursued a career in teaching and research, reaching tenured full professor in 1982. Taught courses in

Physical Chemistry, Biochemistry, and Biophysics, and supervised numerous PhD and MS thesis

committees in the physical sciences. My research group determined several protein crystal structures

using X-ray crystallography and authored pioneering papers on biological electron transfer mechanisms,

principles of protein architecture, and role of dynamics in protein function. My research was supported

through competitively funded federal research grants from the National Institutes of Health (NIHGMS),

National Science foundation (NSF), and the Research Corporation.

July 18, 2012 Page 4 of 13

F. R. Salemme, PhD Resume

Yale University New Haven, CT

Visiting Associate Professor 1981-1982

Molecular Biophysics and Biochemistry

During 1981-1982 I was on Sabbatical leave at Yale University.

Worked with members of the Yale WERMS structural biology and biophysics group.

Developed pioneering computer methods for the computation, analysis, and display of 3D protein

electrostatic fields.

Carried out theoretical studies of protein-DNA interactions.

Developed normal mode approximation of cooperative dynamics in protein secondary structures.

EDUCATION

University of California at San Diego La Jolla, CA

Postdoctoral Fellow, Biochemistry 1972-1973

M.S., Ph.D., Chemistry 1968-1972

I received a Ph.D. in Chemistry under the direction of Joseph Kraut in 1972, for X-ray structural studies of

cytochrome c2, one of the first protein structures to be determined at near atomic resolution.

Thesis Title: "Structure of Cytochrome c2 of Rhodospirillum rubrum at 2.0 Resolution and Related

Topics in Protein Crystallography."

Postdoctoral work with M.D. Kamen on electron transport mechanisms.

Designed and constructed (with Stanley Miller) UCSD steam-powered car for CalTech-MIT coast-to-

coast clear air car race.

Yale University New Haven, CN

B.A., Molecular Biophysics 1962/63 - 1965/67

with exceptional distinction

Admitted to MIT and Yale from Junior year in high school, 1962.

Clow Scholarship, Yale University, 1963.

Built X-ray instrumentation for Harold Wyckoff and Fred Richards as undergraduate student.

Scholar of the House, Yale University, 1967.

Devane Senior Prize for research work on "Chemical Modification of Ribonuclease-S" with F.M.

Richards, 1967.

Lamont Geological Observatory Palisades, NY

Shipboard Scientist 1964

Research Vessel, Robert D. Conrad

Served as shipboard scientist and able-bodied seaman aboard oceanographic research vessel Robert D.

Conrad (AGOR-3). The cruise circumnavigated the earth (~70,000 nautical miles) to map tectonic plate

boundaries and perform seismic profiling and deep core sampling of geological features on the ocean

floor.

Designed, built and operated instrumentation for deep water oceanographic studies.

Supervised deep water equipment recovery and emergency shipboard rigging operations.

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F. R. Salemme, PhD Resume

PROFESSIONAL & INTERESTS

BUSINESS ADVISORY & HONORS:

BioLeap (A biotechnology company engaged in structure-based drug design) Advisory Board (2008-)

Biotechnology Greenhouse of Southeastern Pennsylvania Advisory Committee (2002-2003)

Nuventive Inc. (An information technology company) Advisory Board (2001-2008)

InforMax (A bioinformatics company) Scientific Advisory Board (2000-2002)

Philadelphia Business Journal Fast Fifty Growth Company-3DP (2001)

Ernst & Young Entrepreneur of the Year Award-Greater Philadelphia (To 3DP) (1998)

Ernst & Young Entrepreneur of the Year Finalist-Greater Philadelphia (To 3DP) (1996-1997)

Philadelphia Technology Council Enterprise Award Finalist (To 3DP) (1995)

SCIENTIFIC ADVISORY & HONORS:

Chair, NIH Review Committee on Protein Structure Initiative Knowledge Base (2009)

Hauptman Woodward Medical Research Institute Board of Advisors (2008-)

Chair, NIH Review Committee on Drug Docking and Screening Data Resource (2008)

Rutgers University Guest Lecturer (2007)

Yale University Medical School Guest Lecturer (2005, 2006)

NIH National Center for Biotechnology Information PubChem Advisory Board (2004-2009)

NIH NCBI Board of Scientific Counselors (2004-2009)

National Cancer Institute Special Review Committee for Chemical Genomics (2004)

Editorial Board, Assay and Drug Development Technologies (2004-)

National Center for Biotechnology Information (NIH NCBI NLM) Advisory Committee (2003)

Biophysical Society Finance Committee (2002-2005)

Penn State Nanofabrication Manufacturing Partnership Advisory Board (2001-)

NIST Visiting Committee (1999-2006)

Princeton University Guest Lecturer (1999-2004)

Member, NIH Special Study Section on the Protein Structure Initiative (1999, 2005)

Program Organizer, University of Delaware Engineering Outreach Program (1998-1999)

Princeton University Visiting Research Collaborator (1993-1996)

Chemical Science and Technology Panel, NIST NAS/NRC Board of Assessment (1992-1993)

North Carolina Supercomputing Center Resource Advisory Committee (1992-1995)

Editorial Board, STRUCTURE (1992-1994)

Editorial Board, PROTEINS: Structure, Function,Genetics (1991-1996)

Member, US National Academy of Sciences-USSR Workshop on Proteins and Glasses (1991)

Keck Center for Computational Biology Scientific Advisory Board, Baylor Medical College and Rice

University, (1990-1993)

Editor, Protein Engineering and Design, Current Opinion in Structural Biology (1990-92)

NIH Review Committee on "Structural Biology for Targeted Drug Design for AIDS" (1987, 1992)

Princeton University Department of Chemistry Advisory Board (1987-93)

NASA Space Sciences Applications Committee (1986-87)

Brookhaven Protein Data Bank Advisory Committee (1985-96)

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F. R. Salemme, PhD Resume

NASA Macromolecular Crystallography Center (UAB Birmingham) Advisory Board (1985-93)

Co-Organizer, Gordon Research Conference on Diffraction Methods in Molecular Biology (1985)

Biophysics Review Panel, National Science Foundation (1983-86)

NIH Study Section on Biochemistry and Biophysics, Special Member (1982).

Special Reviewer, Biological Synchrotron Studies at SLAC (Stanford), CHESS (Cornell), and NSLS

(Brookhaven National Labs) (1981-93).

NIH Special Study Section Member (Large-Scale Computer and Synchrotron Resources) (1980-96)

Camille and Henry Dreyfus Teacher-Scholar Award (1978)

U.S. Public Health Service Predoctoral Fellow (1967-72)

Devane Senior Prize, Yale University (1967)

Scholar of the House, Yale University (1967)

PATENTS & PUBLICATIONS

PATENTS: 34 Issued US Patents (F. R. Salemme and Other Co-Inventors)

Use of a TRPM5 Inhibitor to Regulate Insulin and GLP-1 Release. US Patent No. 8,193,168

[06.05.12]

Compositions And Methods For Producing A Salty Taste In Foods Or Beverages. US Patent No.

7,455,872 [11.25.08]

Compositions And Methods For Producing Flavored Seasonings That Contain Reduced Quantities

Of Common Salt. US Patent No. 7,452,563 [11.18.08]

System, Method and Computer Program Product for Fast and Efficient Searching of Large

Chemical Libraries. US Patent No. 7,188,055 [10.26.08]

Method, System and Computer Program for Displaying Chemical Data. US Patent No. 7,188,055

[03.06.07]

Method, System and Computer Program Product for Representing Object Relationships in a Multi-

Dimensional Space. US Patent No. 7,139,739 [11.21.06]

High Throughput Method for Functionally Classifying Proteins Identified using a Genomics

Approach. US Patent No. 7,122,321 [10.17.06]

Method, System, and Computer Program Product for Non-linear Mapping of Multi-Dimensional

Data. US Patent No. 7,117,187 [10.03.06]

Method, System and Computer Program for Analyzing Combinatorial Libraries. US Patent No.

7,054,757 [05.30.06]

System, Method and Computer Program Product for Representing Object Relationships in Multi-

Dimensional Space. US Patent No. 7,039,621 [05.02.06]

Microtiter Plate with Integral Heater US Patent No. 6,940,055 [09.06.05]

Microplate Thermal Shift Assay Apparatus for Ligand Development and Multi-variable Protein

Chemistry Optimization. US Patent No. 6,849,458 [02.01.05]

Method, System, and Computer Program Product for Determining Properties of Combinatorial

Library Products from Features of Library Building Blocks. US Patent No. 6,834,239 [12.21.04]

Method, System, and Computer Program Product for Encoding and Building Products of a Virtual

Combinatorial Library. US Patent No. 6,678,619 [01.13.04]

Method and Computer Program Product for Designing Combinatorial Arrays. US Patent No.

6,671,627 [12.30.03]

Method, System and Computer Program Product for Non-Linear Mapping of Multi-Dimensional

Data. US Patent No. 6,571,227 [05.27.03] [Algorithms for mapping multidimensional data sets]

Microplate Thermal Shift Assay For Ligand Development using 5'(4"Dimethylamino-Phenyl)-2-(4'-

Phenyl) Oxazole Derivative Fluorescent Dyes. US Patent No. 6,569,631 [05.27.03]

July 18, 2012 Page 7 of 13

F. R. Salemme, PhD Resume

System, Method, and Computer Program Product for Representing Proximity Data in a Multi-

Dimensional Space. US Patent No. 6,453,246 [09.17.02]

Systems and Methods for Integrating Heaters with Microtiter Plates. No. 6,423,948 [07.23.02]

Method of Generating Chemical Compounds Having Desired Properties. US Patent No. 6,421,612

[07.16.02]

Method For Identifying Lead Compounds. US Patent No. 6,303,322 [01.16.01]

Method, System, and Computer Program Product for Representing Similarity/Dissimilarity Between

Chemical Compounds. US Patent No. 6,295,514 [09.25.01]

Method For Identifying Conditions That Facilitate Recombinant Protein Folding. US Patent No.

6,291,192 [09.18.01]

Microplate Thermal Shift Assay for Ligand Development and Multi-Variable Protein Chemistry

Optimization. US Patent No. 6,291,191 [09.18.01]

Method For Determining Conditions That Facilitate Protein Crystallization. US Patent No. 6,268,158

[07.31.01]

Method For Sensing and Processing Fluorescence Data for Multiple Samples. US Patent No.

6,268,218 [7.31.01]

Method For Determining Conditions That Stabilize Proteins. US Patent No. 6,232,085 [05.15.01]

Microplate Thermal Shift Assay Apparatus for Ligand Development and Multi-Variable Protein

Chemistry Optimization. US Patent No. 6,214,293 [04.10.01]

Microplate Thermal Shift Assay Apparatus for Ligand Development and Multi-Variable Protein

Chemistry Optimization. US Patent No. 6,036,920 [03.14.00]

Microplate Thermal Shift Assay for Ligand Development and Multi-Variable Protein Chemistry

Optimization. US Patent No. 6,020,141 [02.01.00]

System, Method and Computer Program Product For At Least Partially Automatically Generating

Chemical Compounds with Desired Properties from a List of Potential Chemical Compounds to

Synthesize. US Patent No. 5,901,069 [05.04.99]

System, Method and Computer Program Product For At Least Partially Automatically Generating

Chemical Compounds Having Desired Properties. US Patent No. 5,684,711 [11.04.97]

System and Method of Automatically Generating Chemical Compounds with Desired Properties. US

Patent No. 5,574,656 [11.12.96]

System and Method of Automatically Generating Chemical Compounds with Desired Properties. US

Patent No. 5,463,564 [10.31.95]

PUBLICATION SUMMARY: 80+ Scientific Journal Articles, Invited Reviews, & Book Chapters

Topic Areas:

Drug Discovery: Structure-Based Design, Chemi-Informatics, Computer-Directed

Combinatorial Chemistry, & Chemical Genomics

Computer Modeling & Molecular Dynamics Simulations of Complex Biological Systems

Nanotechnology, Molecular Electronics, Biomaterials, & Protein Engineering

Biological Electron Transfer Mechanisms & Protein Electrostatics

Protein Structure Determination by X-Ray Crystallography

Includes Publications in Nature (5), Science (5), Proceedings of the National Academy of

Sciences (5), Journal of Molecular Biology (7), Journal of Biological Chemistry (3), Journal

of the American Chemical Society (2), Medicinal Chemistry Research (2), Cell,

Biochemistry, Structure and others.

July 18, 2012 Page 8 of 13

F. R. Salemme, PhD Resume

SELECTED PUBLICATIONS OF F. RAYMOND SALEMME, PHD

Drug Discovery: Structure-Based Drug Design, Computer-Directed Combinatorial Chemistry,

Biophysical Drug Screening

Summary: These papers represent the evolution of scientific understanding and technology for

integration of biophysical methods, computer-directed combinatorial chemistry and protein 3D

structure for drug discovery.

Quantitative Assessment Of TRPM5-Dependent Oral Aversiveness Of Pharmaceuticals

Using A Mouse Brief-Access Taste Aversion Assay, Devantier HR, Long DJ, Brennan FX,

Carlucci SA, Hendrix C, Bryant RW, Salemme FR, Palmer RK, Behavioural Pharmacology 2008;

19(7):673-82

Biochemical Bitter Blocking for New Drug Formulations, Salemme FR, Drug Delivery

Technology. 2008; Vol 8 No 6: 28-33

A Comparison of the Chemical Properties of Drugs and FEMA/FDA Notified GRAS

Chemicals used in the Food Industry, Sprouse DE and Salemme FR, Food and Chemical

Toxicology. 2007; 45:1419-1427

Decrypting the Biochemical Function of an Essential Gene from Streptococcus

pneumoniae using Thermofluor Technology, Carver TE, Bordeau B, Cummings MD, Petrella EC,

Pucci MJ, Zawadzke LE, Dougherty BA, Tredup JA, Bryson JW, Yanchunas J Jr, Doyle ML, Witmer MR,

Nelen MI, Desjarlais RL, Jaeger EP, Devine H, Asel ED, Springer BA, Bone R, Salemme FR, Todd M. J

Biol Chem. 2005; 280:117**-*****

Thermodynamic Stability Of Carbonic Anhydrase: Measurements Of Binding Affinity And

Stoichiometry Using Thermofluor, Matulis D, Kranz JK, Salemme FR, & Todd MJ Biochemistry

2005; 44(13): 5258-66.

Chemical Genomics as an Emerging Paradigm for Postgenomic Drug Discovery. F.R.

Salemme, Pharmacogenomics. 2003; 4(3):257-267

Direct Binding Assays for Pharma Screening. M.J. Todd & F.R. Salemme, Genetic

Engineering News. 2003;3:28-29

Applications of Calorimetric Methods to Drug Discovery and the Study of Protein

Interactions. P.C. Weber & F.R. Salemme, Curr. Opinion in Structural Biol. 2003; 13:115-121

Combinatorial Informatics in the Post-Genomics Era, D. Agrafiotis, V. Lobannov, F.R.

Salemme Nature Drug Discovery. 2002; 1:338-346

High Density Miniaturized Thermal Shift Assay as a General Strategy for Drug Discovery,

M.P. Pantoliano, E. Petrella, J. Kwasnoski, V. Lobannov, J. Myslik, E. Graf, T. Carver, E. Asel, B.

Springer, F.R. Salemme Journal of Biomolecular Screening. 2001; 6(6):492-440

Structure-Activity and Crystallographic Analysis of a New Class of Non-amide-Based

Thrombin Inhibitor. Lu, T., Soll, R. M., Illig, C., Bone, R., Murphy, L., Spurlino, J., Salemme, F. R.,

& Tomczuk, B., Bioorganic & Med. Chem. Lett. 2000; 10:79-82.

Non-Peptidic Phenyl-Based Thrombin Inhibitors: Exploring Structural Requirements of

the S1 Specificity Pocket with Amidines. Lu, T., Tomczuk, B., Bone, R., Murphy, L., Salemme, F.

R., & Soll, R. M., Bioorganic & Med. Chem. Lett. 2000; 10:83-85.

Amidinohydrazones as Guanidine Bioisosteres: Application to a New Class of Potent,

Selective, and Orally Bioavailable, Non-amide-Based Small Molecule Thrombin Inhibitors.

Soll, R. M., Lu, T., Tomczuk, B., Illig, C., Fedde, C., Eisennagel, S., Bone, R., Murphy, L., Spurlino, J.,

& Salemme, F. R., Bioorganic & Med. Chem. Lett. 2000; 10:1-4.

Advances in diversity profiling and combinatorial series design. Agrafiotis, Dimitris K.; Myslik,

James C.; Salemme, F. Raymond, Molecular Diversity 1999; 4(1):1-22.

Serine proteases-directed small molecule probe libraries. Dhanoa, D. S.; Soll, R.M.;

Subasinghe, N. Wu, Z., Rinker, J., Hoffman, J., Eisennagel, S., Graybill, T., Bone, R., Radzicka, A.,

Murphy, L., Salemme, F. R., Med. Chem. Res. 1998; 8(4/5): 187-205.

July 18, 2012 Page 9 of 13

F. R. Salemme, PhD Resume

SELECTED PUBLICATIONS OF F. RAYMOND SALEMME, PHD (Continued 2)

Expanding the envelope of structure-based drug design using chemical libraries:

application to small-molecule inhibitors of thrombin. Illig, C., Eisennagel, S., Bone, R.,

Radzicka, A., Murphy, L., Randle, T., Spurlino, J., Jaeger, E., Salemme, F. R., Soll, R. M., Med.

Chem. Res. 1998; 8(4/5): 244-260.

In vitro evaluation and crystallographic analysis of a new class of selective, non-amide-

based thrombin inhibitors. Lu, T., Tomczuk, B., Illig, C. R., Bone, R., Murphy, L., Spurlino, J.,

Salemme, F. R., Soll, R. M., Bioorg. Med. Chem. Lett. 1998; 8(13): 1595-1600.

Serendipity meets precision: the integration of structure-based drug design and

combinatorial chemistry for efficient drug discovery. Salemme, F. R., Spurlino, J., & Bone, R

Structure 1997; 5: 319-324.

The Integration of Structure-Based Design and Directed Combinatorial Chemistry for

New Pharmaceutical Discovery. Bone, R., & Salemme, F. R., Structure-Based Drug Design,

Veerapandian, P., Ed.; Marcel Dekker, Inc.: New York, 1997; 525-539.

Structure-Based Design of Synthetic Azobenzene Ligands for Streptavidin, P. C. Weber, M.

W. Pantoliano, D. M. Simons, & F. R. Salemme J. Amer. Chem. Soc., 1994; 116: 2717-2724.

Crystallographic and Thermodynamic Comparison of Natural and Synthetic Ligands

Bound to Streptavidin, P.C. Weber, J.J. Wendoloski, M.W. Pantoliano, and F.R. Salemme J.

Amer. Chem. Soc. 1992; 114: 3197-3200.

Computational Challenges in Structure-Based Drug Design, J.J. Wendoloski and F.R.

Salemme Cray Channels, 1990; 11: 2-5

Structural Genomics

Summary: These papers describe pioneering studies defining the origins of the major structural

classifications of proteins, and the factors that are responsible for their structural stability. In

contrast to contemporaneous descriptive work on comparative structural analysis of proteins, my

studies were characterized detailed 3D coordinates of representative structures generated through

computer modeling.

Neural Network for the Detection and Prediction of 3D Structural Motifs in Proteins L.D.

Greller, Evan W. Steeg & F. R. Salemme Math Modeling and Sci. Computing 1993; 2: 630-

635.

Structural Properties of Protein -Sheets, F.R. Salemme, Progress in Biophysics and

Molecular Biology 1983; 42: 95-133

Conformational Flexibility and Amide Exchange Stability in Protein -Sheets, F.R.

Salemme, Nature 1982; 299: 754-756

The -Helix Dipole Model and Electrostatic Stabilization of a 4- -Helical Proteins, R.

Sheridan, R.M. Levy, and F.R. Salemme, Proc. Natl. Acad. Sci. USA 1982; 79: 4545-4549.

On the Evolutionary Relationship of 4- -Helical Heme Proteins, P. C. Weber, F.R. Salemme,

P. Bethge, and F.S. Matthews J. Biol. Chem. 1981; 256: 7702-7704.

Conformational and Geometrical Properties of -Sheets in Proteins. I. Parallel Sheets,

F.R. Salemme and D.W. Weatherford, J. Mol. Biol. 1981; 146: 101-117.

Conformational and Geometrical Properties of -Sheets in Proteins. II. Antiparallel and

Mixed -Sheets, F.R. Salemme and D.W. Weatherford, J. Mol. Biol. 1981; 146: 119-141.

Conformational and Geometrical Properties of -Sheets in Proteins. III. Isotropically

Stressed Configurations, F.R. Salemme, J. Mol. Biol. 1981; 146: 143-156.

Structural and Functional Diversity in 4- -Helical Proteins, P.C. Weber & F.R. Salemme,

Nature 1980; 287: 82-84.

July 18, 2012 Page 10 of 13

F. R. Salemme, PhD Resume

SELECTED PUBLICATIONS OF F. RAYMOND SALEMME, PHD (Continued 3)

Conformations of Twisted Parallel -Sheets and the Origin of Chirality in Protein

Structures, D.W. Weatherford & F.R. Salemme, Proc. Natl. Acad. Sci. USA 1979; 76: 19-23.

Structural Convergence During Protein Evolution, F.R. Salemme, M.D. Miller, and S.R. Jordan,

Proc. Natl. Acad. Sci. USA 1977; 74: 2820-2824.

Computer Modeling & Molecular Dynamics Simulations of Complex Biological Systems

Summary: These papers represent major computational studies of interacting biological systems.

The large-scale molecular dynamics simulations of electron transfer complexes, phospholipid micelles,

and bioelastomers were the first of their kind and among the largest computational simulations of

biological systems attempted at the time of publication.

PROBIT: A Statistical Approach to Modeling Proteins from Partial Coordinate Data Using

Substructure Libraries, J.J. Wendoloski & F.R. Salemme J. Molecular Graphics 1992; 10: 124-

126.

A Molecular Dynamics Investigation of the Elastomeric Restoring Force in Elastin, Z.W.

Wasserman and F.R. Salemme, Biopolymers 1990; 29: 1613-1631.

FRAGLE: Modeling with Substructure Libraries Derived from Known Protein Structures,

Finzel, BC, Kimatian S, Ohlendorf, DH, Wendoloski, JJ, Levitt M, Salemme FR, In Crystallographic and

Modeling Methods in Molecular Design (S Ealick & C Bugg eds.) Springer Verlag, New York, 175-189

(1990)

Molecular Dynamics Simulation of a Phospholipid Micelle, J.J. Wendoloski, S. Kimatian, C.E.

Schutt, F.R. Salemme, Science 1989; 243: 636-638.

Competitor Analogues for Defined T Cell Antigens Incorporating a Putative Binding Motif

and Polyproline and Polyglycine Spacers, J. Maryanski, A. Verdini, P.C. Weber, F.R. Salemme,

G. Corradin, Cell 1989; 60: 63-72.

The Identification of Tyrosine as a Common Key Residue in Unrelated H-2Kd Restricted

Antigenic Peptides, J. Maryanski, P. Romero, A. Van Pel,, T. Boon, F.R. Salemme, J-C Cerrotitini,

G. Corradin, International Immunology 1991; 3: 1035-1042.

Molecular Dynamics of a Cytochrome c-Cytochrome b5 Electron Transfer Complex, J.J.

Wendoloski, J.B. Matthew, P.C.Weber, and F.R. Salemme, Science 1987; 238: 794-796.

Computer Simulations of Biological Interactions and Reactivity, J.J. Wendoloski, Z.

Wasserman, F.R. Salemme, J. Computer Aided Molecular Design 1987; 1: 313-322.

A Model for Catabolite Activator Protein Binding to Supercoiled DNA,

F.R. Salemme Proc. Natl. Acad. USA 1982; 79: 5263-5268

Molecular Electronics, Biomaterials, & Protein Engineering

Summary: At DuPont Central Research and Development Department, several initiatives were

undertaken to use engineered proteins for improved biopharmaceuticals as well as for new

technological applications in advanced materials and molecular electronics.

Design, Synthesis, and Fabrication of a Novel, Self-Assembling Fibrillar Protein, J. P.

O'Brien, R.H. Hoess, K.H. Gardner, R.L. Locke, Z. R. Wasserman, P. C. Weber, & F. R. Salemme in

Silk Polymers : Materials Science and Biotechnology (D. Kaplan, W.W. Adams, B. Farmer, C.

Viney, eds.) 1994; ACS Symposium Series 55: 104-117.

Permuteins of interleukin 1 : A simplified approach for the construction of permuted

proteins having new termini R. A. Horlick, H. J. George, G. M. Cooke, R. J. Tritch, R. C.

Newton, A. Dwivedi, M. Lischwe, F. R. Salemme, P. C. Weber, and Horuk, R. Protein Engineering

1992; 5: 427-431.

Current

Protein Engineering for Molecular Electronics, S. L. Sligar & F. R. Salemme

Opinion in Structural Biology 1992; 2: 587-592.

July 18, 2012 Page 11 of 13

F. R. Salemme, PhD Resume

SELECTED PUBLICATIONS OF F. RAYMOND SALEMME, PHD (Continued 4)

Protein Engineering for Fabrication of BioMolecular Electronic Devices, F.R. Salemme, in

Soviet and East European Research Related to Molecular Electronics, FASAC Report 1990.

Structural Polymorphism in Transmembrane Channels, F.R. Salemme, Science 1988; 241:

145 & 190.

Some Design Principles for Structurally Stable Proteins, D.H. Ohlendorf, B.C.Finzel,

P.C.Weber, and F.R.Salemme, in Protein Engineering (D.L.Oxender, C.F. Fox, Eds.) Alan R. Liss,

Inc., NY, NY. 1987; 165-173.

Engineering Aspects of Protein Structure, F.R. Salemme, Ann. New York Acad. Sciences

1985; 439: 97-106.

Biological Electron Transfer Mechanisms & Protein Electrostatics

Summary: My work in the structure of electron transfer proteins established fundamental principles

of biological electron transfer, including specifically, 1) the role of complementary electrostatic

interactions in the facilitation of most biological transfer interactions between reversibly interacting

electron transfer proteins, and 2) that biological electron transfer took place by facilitated electron

tunneling, as opposed to classical outer sphere electron transfer mechanisms common for non-

biological metal complexes in solution.

Electrostatic Orientation During Electron Transfer Between Flavodoxin and Cytochrome

c, J.B. Matthew, P.C. Weber, F.R. Salemme, and F.M. Richards, Nature 1983; 301: 169-171

Transient Kinetics of Electron Transfer Reactions of Flavodoxin: Ionic Strength

Dependence of Semiquinone Oxidation by Cytochrome c, Ferricyanide, and Ferri EDTA

and Computer Modelling of Reaction Complexes, R.P. Simondsen, P.C. Weber, F.R. Salemme,

and G. Tollin, Biochemistry 1983; 21: 6366-6375.

Structure and Function of Cytochrome c, F.R. Salemme, Annual Review of Biochemistry

1977; 46: 229-329.

A Hypothetical Structure for an Intermolecular Electron Transfer Complex of

Cytochromes c and b5, F.R. Salemme, J. Mol. Biol. 1976; 102: 563-568.

Structural Bases for Function in Cytochrome c: An Interpretation of Comparative X-ray

and Biochemical Data, F.R. Salemme, J. Kraut, and M.D. Kamen, J. Biol. Chem. 1973; 248:

7701-7716.

Protein Structure Determination by X-Ray Crystallography

Summary: During my undergraduate work with Fred Richards at Yale, I worked on one of the first

3D protein structures determined by X-ray crystallography. (In 2001 there are approximately 12,000

known 3D protein structures.) Subsequently, I have continued to develop and use X-ray

crystallography to investigate protein structure and function, and as a key component for protein

engineering and drug discovery.

Structural Studies of the Retroviral Proteinase from Avian Myeloblastosis Associated

Virus, D.H. Ohlendorf, S.I. Foundling, J.J. Wendoloski, G. Sedlacek, P. Strop, and F.R. Salemme

Proteins: Structure, Function,Genetics 1992; 14: 382-392.

An Independent Crystallographic Refinement of Porcine Phospholipase A2 at 2.4

Resolution, B.C. Finzel, D.H. Ohlendorf, P.C. Weber, and F.R. Salemme, Acta. Cryst. 1991; B47:

558-559.

The Refined Crystal Structure of Bovine Pro-Phospholipase A2 at 1.6 Resolution, B. C.

Finzel, P.C. Weber, D.H. Ohlendorf, J.J. Wendoloski and F.R. Salemme Acta Cryst. 1991; B47: 814-

816.

Structural Origins of High Affinity Biotin Binding to Streptavidin, P.C. Weber, D.H.

Ohlendorf, J.J. Wendoloski, F.R. Salemme, Science 1989; 243: 85-88

July 18, 2012 Page 12 of 13

F. R. Salemme, PhD Resume

SELECTED PUBLICATIONS OF F. RAYMOND SALEMME, PHD (Continued 5)

Protein Crystal Growth in Microgravity, L.J. DeLucas, C.D. Smith, H.W. Smith, V.K. Senadhi, S.E.

Senadhi,S.E. Ealick, D.C. Carter, R.S., Snyder, P.C. Weber, F.R. Salemme, D.H. Ohlendorf, H.M.

Einspahr, L.L. Clancy, M.A. Navia, B.M McKeever, T.L. Nagabhushan, G. Nelson, A. McPherson, S.

Koselak, G. Taylor, D. Stammers, K. Powell, G. Darby, C.E. Bugg Science 1989; 246: 651-654.

Molecular Factors Stabilizing Protein Crystals, F.R.Salemme, Lars Genieser, B.C. Finzel, R.M.

Hilmer, J.J. Wendoloski, J. Crystal Growth 1988; 90: 273-282.

Use of an Imaging Proportional Counter in Macromolecular Crystallography, A.J. Howard,

G.L. Gilliland, B.C. Finzel, T.L. Poulos, D.H. Ohlendorf, and F.R. Salemme, J. Appl. Cryst. 1987; 20:

383-387

The Structure of Ferricytochrome c' from Rhodospirillum molischianum at 1.67

Resolution, B.C. Finzel, P.C. Weber, K.D. Hardman, and F.R. Salemme, J. Mol. Biol. 1985; 186:

627-643.

Lattice Mobility and Anomalous Temperature Factor Behavior in Cytochrome c, B.C.Finzel

and F.R.Salemme, Nature 1985; 315: 686-688.

The 2 Resolution Structure of a Thermostable Ribonuclease-A Chemically Cross-linked

Between Lysine residues 7 and 41, P.C.Weber, S. Sheriff, D.H. Ohlendorf, B.C. Finzel, and F.R.

Salemme, Proc. Natl. Acad. Sci. USA 1985; 82: 8473-8477.

Structure of Cytochrome c': A Dimeric High-Spin Haem Protein, P. C. Weber, R.G. Bartsch,

M.A. Cusanovich, R.C. Hamlin, A. Howard, S.R. Jordan, M.D. Kamen, T.E. Meyer, D.W. Weatherford,

Ng.H. Xuong, and F.R. Salemme, Nature 1980; 286: 302-304.

Peptide Models for the Study of Coupled Conformational Properties of Protein Secondary

Structures, F.R. Salemme, J. Mol. Biol. 1979; 126: 591-595.

The Structure of Oxidized Cytochrome c2 of Rhodospirillum rubrum, F. R.Salemme, S.T.

Freer, R.A. Alden, Ng.H. Xuong, and J. Kraut. J. Biol. Chem. 1973; 248: 3910-3921.

A Free Interface Diffusion Technique for the Crystallization of Proteins for X-ray

Crystallography, F.R. Salemme, Arch. Biochem. Biophys. 1972; 151: 533-539.

A Device for the Rapid Measurement of Molecular Model Coordinates for X-ray

Crystallography, F.R. Salemme & D.G. Fehr J. Mol. Biol. 1972; 70: 697-700

July 18, 2012 Page 13 of 13

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