David a pearlman
Lexington MA 02421
DAPearlman [AT] gmail.com
Uniquely qualified computational science pioneer with multiple Product Management successes seeks challenging new leadership opportunities
Pioneering computational chemist who has repeatedly taken early stage ideas from germination to success ∎ The only person who can claim primary contributions to three of the biggest computational molecular modeling platforms (AMBER, Schrodinger, Discovery Studio) ∎ Vision to see both big picture and deal with details ∎ Exemplary communications and writing skills, including ability to present technical material to non-technical audiences ∎ Out-of-box thinker able to manage multiple clients in dotted line relationships
ž Product Manager: Developed BioLuminate biologics structure design platform for Schrödinger, from ground up. Most successful product launch in their history. First biologics-focused package on market.
ž Product manager of the very first commercialized molecular modeling package, Discover; Helped launch Biosym Techologies (now Accelrys/Biovia);
ž Product Manager & Director Customer Experience for Cyrus Biotechnology: Providing first commercialization of Rosetta Protein Design as Google based SaaS
ž First author of several versions of Amber (most used molecular modeling package in the world)
ž String of early, seminal publications in field of Free Energy Perturbation (FEP)
ž Nearly 70 publications, majority as primary author, widely cited (ResearchGate score 35)
ž First degree from UC Berkeley in modern computational chemistry
ž First person to provide formal avenue for music promotion on the Internet
ž Helped establish Vertex Pharmaceuticals’ reputation in drug design through prolific publication
DIRECTOR/PRODUCT MANAGER Protein Design platform – Cyrus Biotechnology – 2017 to 2019
Both product manager and director of customer experience for Cyrus Bench
– First successful commercialization of academic Rosetta protein design platform
– Modern SaaS tool using Google Cloud on the backend
– Bridged customer and developer clients, pre-sales, post-sales
– Project management of milestone-based collaborative science with customers
– As member of executive team, helped lead corporate strategy
– Managed customer support team
DIRECTOR/PRODUCT MANAGER biologics software platform – Schrödinger Inc – 2010 to 2017
Successfully created structure-based design platform for biologics/biopharmaceuticals from scratch/vision to market
– Most successful new product launch in Schrödinger history
– Duties include: Overall product strategy; poll customers; write internal white papers; create feature specs; design GUI interfaces; oversee implementation; oversee beta testing and refinement; create internal and external marketing documents; external pre-sales presentations; work closely with sales account managers; triage improvement/bug requests; create roadmaps for new features.
– Adept at generating cross-team internal buy-in, and balancing team, internal and external stakeholders.
– Provide direction for new biologics-related basic research
– Speak at 6-8 relevant conferences per year, dozens pre- and post- sales presentations per year
– Create impactful story at appropriate level that helped open a new market for this product
– Collaborate and publish on basic research related to biologics, including antibody prediction and FEP
– Project management of collaborative science with customers
– Develop collaborative ties to academic laboratories
COMPUTATIONAL CHEMIST III – Broad Institute of MIT & Harvard/Stanley Center – 2007 to 2010
Provide direction and support for all aspects of computational chemistry / molecular modeling for Stanley Center for Psychiatric Research
– Molecular docking campaigns
– Structure-based ligand design
– Develop new methodologies and paradigms to improve efficiency of drug design
CEO – Dapper Research – 2004 to 2007
Development and characterization of high-throughput ligand scoring functions
– FURMASA (simplified function based on an MD grid and a surface area term)
– ZIPAP (molecular scoring function derived from experimental potential of mean force data)
– MM-PBSA (combined molecular mechanics and Poisson-Boltzmann energies)
PRINCIPAL investigator – Vertex Pharmaceuticals – 1991 to 2004
Early employee, hired to be “scientist in residence”, i.e. to publish quality research at a substantial rate, speak publicly, etc. to prove the now-successful company was serious about their new paradigm that elevated the importance of computational chemistry to drug discovery
– Develop new methods for theoretical free energy calculations (FEP/TI)
– Develop new scoring methods for high throughput data mining
– Develop new methods for de novo drug design
– Develop new methods for NMR refinement
– Contribute to internal drug discovery projects
– Contribute as first author to AMBER software package in collaboration with UCSF
Post doctoral assoc / Asst Research chemist – University of California San Francisco – 1987 to 1991
Worked with Peter Kollman. Computational chemistry: Methodology development and application
– First author / primary developer of the AMBER software package, versions 4-5
– Numerous early, defining, methodology papers on free energy calculations (FEP, TI)
– Determination of NMR structures from NOE data, including time-averaged restraints
Discover program leader– Biosym Technologies (now Accelrys/Biovia) – 1985 to 1986
Helped launch company (employee #7). In charge of primary product: Simulation platform Discover. This was the first commercialization of structure-based modeling software.
– Lead commercialization efforts of platform
– Interface with customers, triage requests, road mapping, pre-sales presentations, installations
– Biosym is now Accelrys, acquired by Dassault in 2014 for $750M.
GRADUATE SCHOOL (PH.D.) from University of California, Berkeley (1980-1985)
Advisor: Sung-Hou Kim
Research: Computational studies of DNA systems. Small molecule crystallography to determine charges from high resolution x-ray density. Predict effects of photodamage on DNA. First person to graduate from UC-Berkeley with focus on computational chemistry.
UNDERGRADUATE (B.S.) from Stanford University, Stanford, California (1977-1980)
With distinction, in three years.
1) David A. Pearlman, Stephen R. Holbrook, David H. Pirkle and Sung-Hou Kim (1985) ``Molecular Models for DNA Damaged by Photoreaction.'' Science 227, 1304-1308.
2) David A. Pearlman and Sung-Hou Kim (1985) ``Determinations of Atomic Partial Charges for Nucleic Acid Constituents from X-ray Diffraction Data. I. 2'-Deoxycytidine 5'-Monophosphate.'' Biopolymers 24, 327-357.
3) David A. Pearlman and Sung-Hou Kim (1985) ``The Conformations and Energetics of Photodamaged DNA.'' Proceedings of the International Symposium on Biomolecular Structure and Interactions (Supplement to Journal of Biosciences), 8, 579-592.
4) Sung-Hou Kim, David A. Pearlman, Stephen R. Holbrook and David H. Pirkle (1985) ``Structures of DNA Containing Psoralen Crosslink and Thymine Dimer.'' In: Molecular Basis of Cancer (R. Rein, ed.), pp. 143-152, Alan R. Liss, Inc., New York.
5) David A. Pearlman and Sung-Hou Kim (1985) ``Conformational Studies of Nucleic Acids. I. A Rapid and Direct Method for Generating Furanose Coordinates from the Pseudorotation Angle.'' Journal of Biomolecular Structure and Dynamics 3, 81-98.
6) David A. Pearlman and Sung-Hou Kim (1985) ``Conformational Studies of Nucleic Acids. II. The Conformational Energetics of Commonly Occurring Nucleosides.'' Journal of Biomolecular Structure and Dynamics 3, 99-126.
7) David A. Pearlman, Stephen R. Holbrook and Sung-Hou Kim (1985) ``The Conformational Effects of UV Induced Damage on DNA.'' In: Proceedings of the 18th Jerusalem Symposium on the Interrelationship Among Aging, Cancer and Differentiation (B. Pullman, P.O.P. Ts'o, and E.L. Schneider, eds.), pp. 163-172, D. Reidel Publishing Company, Boston.
8) David A. Pearlman and Sung-Hou Kim (1986) ``Conformational Studies of Nucleic Acids. III. Empirical Multiple Correlation Functions for Nucleic Acid Torsion Angles.'' Journal of Biomolecular Structure and Dynamics 4, 49-68.
9) David A. Pearlman and Sung-Hou Kim (1986) ``Conformational Studies of Nucleic Acids. IV. The Conformational Energetics of Oligonucleotides: d(ApApApA) and ApApApA.'' Journal of Biomolecular Structure and Dynamics 4, 69-98.
10) David A. Pearlman and Sung-Hou Kim, (1988) ``Conformational Studies of Nucleic Acids. V. Sequence Specificities in the Conformational Energetics of Oligonucleotides: The Homo-Tetramers.'' Biopolymers 27, 59-77.
11) Stephen R. Holbrook, David A. Pearlman and Sung-Hou Kim (1988) ``Molecular Models of Photodamaged DNA.'' Reviews of Chemical Intermediates 10, 71-100.
12) Sung-Hou Kim, Milan T. Tomic, David E. Wemmer, David Pearlman and Stephen Holbrook (1988) ``Structure of DNA damaged by UV and psoralen’’ Biochemical Pharmacology 37, 1791.
13) David A. Pearlman and Peter A. Kollman (1989) ``A New Method for Carrying Out Free Energy Perturbation Calculations: Dynamically Modified Windows.'' Journal of Chemical Physics 90, 2460-2470.
14) David A. Pearlman and Peter A. Kollman (1989) ``Free Energy Perturbation Calculations: Problems and Pitfalls Along the Gilded Road.'' In: Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications (W. van Gunsteren and P.K. Weiner, eds.), pp. 101-119, Escom Science Publishers, Netherlands.
15) Wilson S. Ross, Charles C. Hardin, Ignacio Tinoco, Jr., Shashidar N. Rao, David A. Pearlman and Peter A. Kollman (1989) ``Effects of Nucleotide Bromination on the Stabilities of Z-RNA and Z-DNA: A Molecular Mechanics / Thermodynamic Perturbation Study.'' Biopolymers 28, 1939-1958.
16) David A. Pearlman and Peter A. Kollman (1989) ``The Lag Between the Hamiltonian and the System Configuration in Free Energy Perturbation Calculations.'' Journal of Chemical Physics 91, 7831-7839.
17) David A. Pearlman and Sung-Hou Kim (1990) ``Atomic Charges for DNA Constituents Derived from Single-Crystal X-Ray Diffraction Data.'' Journal of Molecular Biology 211, 171-187.
18) David A. Pearlman and Peter A. Kollman (1990) ``The Calculated Free Energy Effects of 5-Methyl Cytosine on the B to Z Transition in DNA.'' Biopolymers 29, 1193-1209.
19) Liem X. Dang, David A. Pearlman and Peter A. Kollman (1990) ``Why Do AT Base Pairs Inhibit Z-DNA Formation?'' Proceedings of the National Academy of Sciences, USA 87, 4630-4634.
20) David A. Pearlman and Sung-Hou Kim (1990) ``Atomic Partial Charges For Nucleic Acids From X-Ray Diffraction Data.'' In: Theoretical Chemistry and Molecular Biophysics (D.L. Beveridge and R.L. Lavery, eds.), pp. 259-270, Adenine Press, New York.
21) David A. Pearlman and Peter A. Kollman (1990) ``Are Free Energy Calculations Necessary? A Comparison of DNA Modeling Studies.'' In: Theoretical Chemistry and Molecular Biophysics (D.L. Beveridge and R.L. Lavery, eds.), pp. 139-152, Adenine Press, New York.
22) David A. Pearlman and Peter A. Kollman (1991) ``The Overlooked Bond-Stretching Contribution in Free Energy Perturbation Calculations.'' Journal of Chemical Physics 94, 4532-4545.
23) Thomas L. James, Miriam Gochin, Deborah J. Kerwood, David A. Pearlman, Uli Schmitz and Paul D. Thomas (1991) ``Refinement of Three-Dimensional Protein and DNA Structures from NMR Data.'' In: Computational Aspects of the Study of Biological Macromolecules by Nuclear Magnetic Resonance Spectrsocopy (J.C. Hoch, F.M. Poulsen and C. Redfield, eds.), pp. 331-347, Plenum Press, New York.
24) David A. Pearlman and Peter A. Kollman (1991) ``Evaluating the Assumptions Underlying Force Field Development and Application, Using Free Energy Conformational Maps for Nucleosides.'' Journal of the American Chemical Society 113, 7167-7177.
25) David A. Pearlman and Peter A. Kollman (1991) ``Are Time-Averaged Restraints Necessary for NMR Refinement? A Model Study for DNA.'' Journal of Molecular Biology 220, 457-479.
26) Naoki Mizushima, David Spellmeyer, Suichi Hirono, David Pearlman and Peter A. Kollman (1991) ``Free Energy Perturbation Calculations on Binding and Catalysis After Mutating Threonine-220 in Subtilisin.'' Journal of Biological Chemistry 266, 11801-11809.
27) Uli Schmitz, David A. Pearlman and Thomas L. James (1991) ``Solution Structure of d(GTATATAC)2 via Restrained Molecular Dynamics Simulations with NMR Constraints Derived from Relaxation Matrix Analysis of 2D NOE Experiments.'' Journal of Molecular Biology 221, 271-292.
28) Mark R. Hurle, Charles D. Eads, David A. Pearlman, George L. Seibel, John Thomason, Phyllis A. Kosen, Peter Kollman, Stephen Anderson and Irwin D. Kuntz (1992) ``Comparison of Solution Structures of Mutant Bovine Pancreatic Trypsin Inhibitor Proteins Using Two-Dimensional Nuclear Magnetic Resonance.'' Protein Science 1, 91-106.
29) David M. Ferguson, David A. Pearlman, William C. Swope and Peter A. Kollman (1992) ``Free Energy Perturbation Calculations Involving Potential Function Changes'' Journal of Computational Chemistry 13, 362-370.
30) Yaxiong Sun, David Spellmeyer, David A. Pearlman and Peter Kollman (1992) ``Simulation of the Solvation Free Energies for Methane, Ethane, and Propane and Corresponding Amino Acid Dipeptides: A Critical Test of the "Bond-PMF" Correction, a New Set of Hydrocarbon Parameters, and the Gas Phase-Water Hyrdophobicity Scale'' Journal of the American Chemical Society 114, 6798-6801.
31) David A. Pearlman (1993) ``Determining the Contributions of Constraints in Free Energy Calculations: Development, Characterization, and Recommendations'' Journal of Chemical Physics 98, 8946-8957.
32) David A. Pearlman and Mark A. Murcko (1993) ``CONCEPTS: A New Dynamic Algorithm for de Novo Drug Suggestion'' Journal of Computational Chemistry 14, 1184-1193.
33) Suresh B. Singh, David A. Pearlman and Peter A. Kollman (1993) ``Free Energy Component Analysis: Application to the "Z-Phobicity" of A*T Base Pairs'' Journal of Biomolecular Structure & Dynamics 11, 303-312.
34) Craig A. Gough, David A. Pearlman and Peter Kollman (1993) ``Calculations of the Relative Free Energies of Aqueous Solvation of Several Fluorocarbons: A Test of the Bond-Potential of Mean Force Correction.'' Journal of Chemical Physics 99, 9103-9110.
35) David A. Pearlman (1994) ``How is an NMR Structure Best Defined? An Analysis of Molecular Dynamics Distance-Based Approaches.'' Journal of Biomolecular NMR 4, 1-16.
36) David A. Pearlman (1994) ``Free Energy Derivatives: A New Method for Probing the Convergence Problem in Free Energy Calculations.'' Journal of Computational Chemistry 15, 105-123.
37) David A. Pearlman (1994) ``A Comparison of Alternative Approaches to Free Energy Calculations'' Journal of Physical Chemistry 98, 1487-1493.
38) Stephen E. Debolt, David A. Pearlman and Peter A. Kollman (1994) ``Free Energy Perturbation Calculations on Parallel Computers – Demonstrations of Scalable Linear Speedup'' Journal of Computational Chemistry 15, 351-373.
39) David A. Pearlman (1994) ``How Well do Time-Averaged J-Coupling Restraints Work?'' Journal of Biomolecular NMR 4, 279-299.
40) Piotr Cieplak, David A. Pearlman and Peter A. Kollman (1994) ``Walking on the Free Energy Hyperspace of the 18-Crown-6 Ion System Using Free Energy Derivatives'' Journal of Chemical Physics 101, 627-633.
41) Christopher A. Lepre, David A. Pearlman, Jya-Wei Cheng, Maureen T. DeCenzo, Robert A. Aldape, David J. Livingston and Jonathon M. Moore (1994) ``Solution structure of FK506 bound to the R42K, H87V double mutant of FKBP-12'' Biochemistry 33, 13571-13580.
42) Susumu Itoh, Maureen T. DeCenzo, David J. Livingston, David A. Pearlman and Manuel A. Navia (1995) ``Conformation of FK506 in X-Ray Structures of its Complexes with Human Recombinant FKBP12 Mutants'' Bioorganic & Medicinal Chemistry Letters 5, 1983-1988.
43) David A Pearlman, David A Case, James W Caldwell, William S Ross, Thomas C Cheatham, Stephen E DeBolt, David M Ferguson, George L Seibel and Peter A Kollman (1995) ``AMBER, a Package of Computer Programs for Applying Molecular Mechanics, Molecular Dynamics and Free Energy Calculations to Simulate the Structural and Energetic Properties of Molecules'' Computer Physics Communications 91, 1-41.
44) Christophe Chipot, Bernard Maigret, David A. Pearlman and Peter A. Kollman (1996) ``Molecular Dynamics Potential of Mean Force Calculations: A Study of the Toluene-Ammonium π-Cation Interactions'' Journal of the American Chemical Society 118, 2998-3005.
45) David A. Pearlman and Patrick Connelly (1995) ``Determination of the Differential Effects of Hydrogen Bonding and Water Release on the Binding of FK506 to Native and Tyr82→Phe82 FKBP-12 Proteins Using Free Energy Simulations'' Journal of Molecular Biology 248, 696-717.
46) David A. Pearlman and Mark A. Murcko (1996) ``CONCERTS: Dynamic connection of fragments as an approach to de novo drug design'' Journal of Medicinal Chemistry 39, 1651-1663.
47) Christophe Chipot, Peter A. Kollman and David A. Pearlman (1996) ``Alternative Approaches to Potential of Mean Force Calculations: Free Energy Perturbation Versus Thermodynamic Integrations--Case Study of some Representative Nonpolar Interactions'' Journal of Computational Chemistry 17, 1112-1131.
48) David A. Pearlman (1996) ``FINGAR: A new genetic algorithm-based method for fitting NMR data'' Journal of Biomolecular NMR 8, 49-66.
49) Christopher A. Lepre, David A. Pearlman, Olga Futer, David J. Livingston and Jonathan M. Moore (1996) ``Practical applications of time-averaged restrained molecular dynamics to ligand-receptor systems: FK506 bound to the Q50R, A95H, K98I triple mutant of FKBP-13 Journal of Biomolecular NMR 8, 67-76.
50) Christophe Chipot, R. Jaffe, Bernard Maigret, David A. Pearlman and Peter A. Kollman (1996) ``Benzene Dimer: A good model for Pi-Pi interactions in proteins. A comparison between the benzene and the toluene dimmers in the CAS phase and in an aqueous solution.'' Journal of the American Chemical Society 118, 11217-11224.
51) David A. Pearlman (1997) ``Applications of Free Energy Calculations to Drug Design.'' In: Thermodynamics and Structure-Based Drug Design (J. Ladbury, P.R. Connelly, eds.), pp. 1-17, R.G. Landes Co., London.
52) Johan Kordel, David A. Pearlman and Walter J. Chazin (1997) ``Protein solution structure calculations in solution: Solvated molecular dynamics refinement of calbindin D-9k.'' Journal of Biomolecular NMR 10, 231-243.
53) David A. Pearlman and B. Govinda Rao (1998) ``Free Energy Calculations: Methods and Applications'' In: The Encyclopedia of Computational Chemistry (P von Rague Schleyer, N L Allinger, T Clark J Gasteiger, P A Kollman, H F Schaefer III and R P Schreiner eds.), John Wiley & Sons, NY, pp. 1036-1061.
54) Thomas Darden, David A. Pearlman and Lee Pederson (1998) ``Ionic charging free energies: Spherical vs. periodic boundary conditions’’ Journal of Chemical Physics 109, 10921-10935.
55) David A. Pearlman (1999) ``Automated Detection of Error Restraints in NMR Data Sets Using the FINGAR Genetic Algorithm Method.'' Journal of Biomolecular NMR 13, 325-335.
56) David A. Pearlman (1999) ``Free energy grids: A practical qualitative application of free energy perturbation to ligand design using the the OWFEG method.'' Journal of Medicinal Chemistry 42, 4313-4324.
57) David A. Pearlman and Paul S. Charifson (2001) ``Improved scoring of ligand-protein interactions using OWFEG free energy grids'' Journal of Medicinal Chemistry 44, 502-511.
58) David A. Pearlman and Paul S. Charifson (2001) ``Are free energy calculations useful in practice? A comparison with rapid scoring functions for the p38 MAP kinase protein system'' Journal of Medicinal Chemistry 44, 3417-3423.
59) David A. Pearlman (2001) ``Free Energy Calculations: Methods for Estimating Ligand Binding Affinities'' In: Free Energy Calculations in Rational Drug Design (M. Rami Reddy and Mark D. Erion eds.) Kluwer Academic/Plenum Publishers, 2001, pp. 9-35.
60) Chris Chipot and David A. Pearlman (2002) ``Free energy calculations. The long and winding gilded road’’ Molecular Simulations 28, 1-12.
61) David A. Pearlman (2005) ``Evaluating the Molecular Mechanics Poisson-Boltzmann Surface Area Method Using a Congeneric Series of Ligands to p38 MAP Kinase’’ Journal of Medicinal Chemistry 48, 7796-7807.
62) David A. Pearlman, B. Govinda Rao and Paul S. Charifson (2008) ``FURSMASA: A new rapid scoring function that uses a MD-averaged potential energy grid and a solvent accessible area term with parameters GA fit to experimental data’’ Proteins: Structure, Function and Bioinformatics 71, 1519-1538.
63) Letian Kuai, Shao-En Ong, Jon M Madison, Xiang Wang, Jeremy R Duvall, Timothy A Lewis, Catherine J Luce, Sean D Conner, David A Pearlman, John L Wood, Stuart L Schreiber, Steven A Carr, Edward M Scolnick and Stephen J Haggarty (2011) ``AAK1 Identified as an Inhibitor of Neuregulin-1/ErbB4-Dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics’’ Chemistry & Biology 18, 891-906.
64) Hege Beard, Anuradha Cholleti, David Pearlman, Woody Sherman and Kathryn A Loving (2013) ``Applying Physics-Based Scoring to Calculate Free Energies of Binding for Single Amino Acid Mutations in Protein-Protein Complexes’’ PLoS ONE 8, e82849.
65) Noeris K Salam, Matvey Adzhigirey, Woody Sherman and David A Pearlman (2014) ``Structure-based approach to the prediction of disulfide bonds in proteins’’ Protein Engineering Design and Selection 10, 365-374.
66) Kai Zhu, Tyler Day, Dora Warshaviak, Colleen Murrett, Richard Friesner and David Pearlman (2014) ``Antibody Structure Determination Using a Combination of Homology Modeling, Energy-Based Refinement and Loop Prediction’’ Proteins Structure Function and Bioinformatics 82, 1646-1655.
67) Sarah Sirin, David A. Pearlman, Woody Sherman (2014) ``Physics-Based Enzyme Design: Predicting Binding Affinity and Catalytic Activity’’ Proteins Structure Function and Bioinformatics 82, 3397-3409.
68) Thomas Steinbrecher, Chongkai Zhu, Lingle Wang, Robert Abel, Christopher Negron, David Pearlman, Eric Feyfant, Jianxin Duan, Woody Sherman (2016) `` Predicting the Effect of Amino Acid Single Point Mutations on Protein Stability–Large Scale Validation of MD-based Relative Free Energy Calculations’’ Journal of Molecular Biology 429, 948-963.
69) Christopher Negron, David A Pearlman, Guillermo del Angel (2019) ``Predicting mutations deleterious to function in beta-lacatamase TEM1 using MM-GBSA’’ PLoS ONE 14 e0214015
70) David A. Pearlman (2019) Ligand binding to Histone Deacetylase HDAC2: using the FURSMASA approach to predict binding efficacy and to probe the assay time dependence of benzamide class ligands (in preparation).