Jacob Durrant: Curriculum Vitae

Jacob D. Durrant

Assistant Professor, University of Pittsburgh

DepartmentOffice
Biological Sciences, University of Pittsburgh103C Clapp Hall
4249 Fifth AvenuePhone: (801) 613-2277
Pittsburgh, Pennsylvania 15260Email: durrantj@nullpitt.edu

Education

University of California San Diego, San Diego, California, 2007-2010

  • Ph.D., Biomedical Sciences
  • Thesis title: “Computational Drug Design Applied To Neglected Disease”
  • Recipient of the Roland K. Robins Pharmacology Dissertation Award

University of California San Diego, San Diego, California, 2005-2007

  • Basic Science Courses, UCSD School of Medicine

Brigham Young University, Provo, Utah, 2004-2005

  • M.S., Physiology and Developmental Biology

Brigham Young University, Provo, Utah, 1998-1999, 2001-2005

  • B.S., Department of Mathematics
  • Phi Kappa Phi, University Honors, Summa Cum Laude
  • Honors thesis title: “An Encompassing Three-Barrier Two-Site Analysis of Gramicidin Conductance Based on Previously Published Conductance Data”

Brigham Young University, Provo, Utah, 1998-1999, 2001-2005

  • B.A., Portuguese Language and Literature
  • Phi Kappa Phi, University Honors, Summa Cum Laude

Research Experience

Assistant Professor, University of Pittsburgh, 2016-present

  • Molecular dynamics simulations and machine learning applied to drug discovery.
  • Large-scale (mesoscale) simulations of whole subcellular environments.
  • Methods-development and application projects (drug discovery, basic science, etc.).

Postdoctoral Researcher (Rommie Amaro), University of California San Diego, 2012-2016

Structure-Based, Computer-Aided Drug Design (CADD)

  • Led efforts to identify novel experimentally verified inhibitors of malarial enoyl-acyl carrier protein reductase, influenza neuraminidase, dihydrofolate reductase, the estrogen receptor, a p53 mutant, S. cerevisiae PMA1, etc.
  • Published a review describing fragment-based CADD.
  • Further developed several CADD software tools, including:
    • NNScore: A machine-learning method for predicting molecular recognition (i.e., a docking rescoring function)
    • POVME: An algorithm for analyzing binding-pocket dynamics.

Molecular Modeling and Simulation

  • Performed extensive molecular dynamics simulations of membrane-embedded influenza glycoproteins. Assembled and simulated an all-atom model of the entire influenza virion coat using available tomographic data. At over 160 million atoms, it is the largest atomistic simulation ever performed.
  • Developed tools for mesoscale atomic-resolution model building (LipidWrapper).
  • Performed simulations of Ebola VP-40, a potential drug target with multiple roles in viral propagation.

Allostery

  • Developed software to computationally identify allosteric pathways using molecular dynamics simulations (WISP).
  • Helped write a review of computational allostery-analysis tools.

Chemoinformatics

  • Developed an automated protocol for identifying known actives from a virtual compound database by mining the online PubChem repository.
  • Created an easy-to-use program to facilitate the sharing of molecular data sets (WebChem Viewer).
  • Gained development skills related to web-based molecular visualization, chemical searching, etc.

Doctoral Student/Postdoctoral Researcher (J. Andrew McCammon), University of California San Diego, 2007-2011

Structure-Based, Computer-Aided Drug Design

  • Successfully identified experimentally validated small-molecule inhibitors of six different protein drug targets.
    • Most were identified by coupling traditional computer-docking techniques with molecular dynamics simulations in order to account for full protein flexibility.
    • I’ve also published several reviews describing these and related methods.
  • Developed and published a number of CADD algorithms
    • NNScore: A neural-network scoring function to predict the binding affinities of protein-ligand complexes. I’m aware of two NNScore-based drug-discovery campaigns that have advanced to the animal-testing phase.
    • AutoGrow: A genetic algorithm to facilitate protein-inhibitor design and optimization.
    • AutoClickChem: A program and online resource for generating novel compound models by performing the reactions of “click chemistry” in silico.
    • BINANA: A program for automatically identifying key ligand-receptor atomic interactions.
    • LigMerge: An algorithm for generating virtual libraries of new compounds by analyzing known ligands.

Molecular Modeling and Simulation

  • Simulated a number of protein drug targets to identify functionally important conformational changes (e.g., transient yet druggable cryptic binding pockets not evident in any crystal structure).
  • Created tools for analyzing molecular dynamics trajectories.
    • POVME: A program to calculate binding-pocket volumes.
    • HBonanza: An algorithm for detecting hydrogen-bond networks.

Chemoinformatics/Target Selection

  • Developed a novel protocol for data mining the Protein Data Bank (PDB) in order to identify secondary targets of a known inhibitor.
  • Published CrystalDock, an algorithm that mines the PDB to identify and position appropriate molecular fragments into novel binding pockets.

Masters Student (David Busath), Brigham Young University, 2003-2005

  • Developed a kinetic model to describe ion conductance through the gramicidin channel.
  • Explored the impact of chemical modifications to that channel on different elements of channel conductance.

Undergraduate Student (Eric Jellen), Brigham Young University, 2002-2003

  • Developed an algorithm for analyzing genetic linkages affected by heterozygous translocations (QuadMap)

Teaching Experience

University of California San Diego, San Diego, California
Instructor, National Biomedical Computation Resource, Summer Institute9/2015
Curriculum Development, in collaboration with Indiana University-Purdue University Indianapolis4/2013 – present
Instructor, National Biomedical Computation Resource, Summer Institute8/2012
Graduate-Student Mentor, McCammon Lab6/2009 – 10/2011
Undergraduate-Student Mentor, McCammon Lab1/2009 – 4/2011
Undergraduate-Student Mentor, McCammon Lab2/2009 – 8/2009
Teaching Assistant, Salk Mobile Lab1/2009 – 5/2009
Brigham Young University, Provo, Utah
Teaching Assistant, Physiology1/2005 – 4/2005
Teaching Assistant, Genetics9/2003 – 12/2003
Teaching Assistant, Genetics7/2003 – 8/2003
Teaching Assistant, Genetics9/2002 – 12/2002
Teaching Assistant, Calculus8/2001 – 12/2001

Awards

YearDescription
2014I led the writing and development of an NSF Petascale Computing Resource Allocation (PRAC) proposal. We were eventually awarded 6 million node-hours (worth an estimated $2.4 million), dedicated exclusively to one of my projects.
2014I co-authored a poster that received a Certificate of Achievement for Outstanding Research (Best Poster) at the “Genomic Technologies and Biomaterials for Understanding Disease” conference, sponsored by Nature.
2014I won the American Chemical Society’s Computers in Chemistry (COMP) Image Competition. My image, which depicted influenza infection, was based on one of my large-scale atomistic models. The prize was a Tesla K40 graphics card, worth ~$5,500 at the time.
2013-2014I provided critical input that led to the awarding of 4.8 million computer service units on the Stampede supercomputer (XSEDE), worth roughly $240,000. This computer time is also dedicated exclusively to one of my projects.
2013-2014I made substantial contributions to an NIH P41 renewal proposal that was recently funded ($9 million). This grant will support a number of projects, including some that focus on anti-neoplastic drug design.
2012I made important contributions to an NSF XSEDE proposal that was eventually awarded 16 million computer service units, which collectively have an estimated dollar value of $800,000.
2010Roland K. Robins Pharmacology Dissertation Award ($500)
2010I was awarded a Texas Advanced Computer Center Startup Project Allocation (175,000 computer service units): “Malarial Protein Target Identification through Virtual Screening.”
2009-2010I received an NIH T32 Pharmacological Sciences Training Grant ($44,600)
2009Research I designed with an undergraduate was selected by the American Society for Cell Biology (ASCB) as one of ten projects out of four thousand considered “novel and newsworthy.” The project was presented at the ASCB conference and was featured in their press book distributed to journalists.
2009Scholarship for a Medicinal Chemistry Intensive Course ($1,745)
2005-2006Federal MSTP Grant (NIH T32; tuition and stipend), UCSD. (~$63,000)
2006Medical School Interview Travel Expenses Grant, Brigham Young University. ($1,500)
1998-1999, 2001-2004Full Tuition Scholarship, Brigham Young University. ($10,000)
2003ORCA Grant, Brigham Young University. ($1,500)
Edwin Hinckley Scholarship, Brigham Young University. ($4,000)
Spring-Summer Scholarship, Brigham Young University. ($1,750)

Publications

  1. Goldgof, G. M.; Durrant, J. D.; Ottilie, S.; Vigil, E.; Allen, K. E.; Gunawan, F., et al. Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor. Sci Rep. 2016, 6, 27806.
  2. Durrant, J. D.; Bush, R. M.; Amaro, R. E. Microsecond Molecular Dynamics Simulations of Influenza Neuraminidase Suggest a Mechanism for the Increased Virulence of Stalk-Deletion Mutants. J Phys Chem B. 2016.
  3. Wagner, J. R.; Lee, C. T.; Durrant, J. D.; Malmstrom, R. D.; Feher, V. A.; Amaro, R. E., et al. Emerging Computational Methods for the Rational Discovery of Allosteric Drugs. Chem. Rev. 2016, 116 (11), 6370.
  4. Durrant, J. D.; Carlson, K. E.; Martin, T. A.; Offutt, T. L.; Mayne, C. G.; Katzenellenbogen, J. A.; Amaro, R. E. Neural-Network Scoring Functions Identify Structurally Novel Estrogen-Receptor Ligands. J. Chem. Inf. Model. 2015, 55 (9), 1953-61.
  5. Scott, W. L.; Denton, R. E.; Marrs, K. A.; Durrant, J. D.; Samaritoni, J. G.; Abraham, M. M.; Brown, S. P.; Carnahan, J. M.; Fischer, L. G.; Glos, C. E.; Sempsrott, P. J.; O’Donnell, M. J. Distributed Drug Discovery: Advancing Chemical Education through Contextualized Combinatorial Solid-Phase Organic Laboratories. J. Chem. Educ. 2015, 92 (5), 819.
  6. Singharoy, A.; Chandler, D.; Durrant, J. D.; Sener, M.; Amaro, R.; Schulten, K. The Do’s and Do Not’s of a 100 Million Atom Molecular Dynamics Simulation. Biophys. J. 2015, 108 (2), 158a.
  7. Ikram, N. K.; Durrant, J. D.; Muchtaridi, M.; Zalaludin, A. S.; Purwitasari, N.; Mohamed, N.; Rahim, A. S.; Lam, C. K.; Normi, Y. M.; Rahman, N. A.; Amaro, R. E.; Wahab, H. A. A virtual screening approach for identifying plants with anti H5N1 neuraminidase activity. J. Chem. Inf. Model. 2015, 55 (2), 308.
  8. Durrant, J. D.; Amaro, R. E. Machine-Learning Techniques Applied to Antibacterial Drug Discovery. Chem. Biol. Drug Des. 2014, 85 (1), 14.
  9. Tallorin, L.; Durrant, J. D.; Nguyen, Q. G.; McCammon, J. A.; Burkart, M. D. Celastrol inhibits Plasmodium falciparum enoyl-acyl carrier protein reductase. Bioorg. Med. Chem. 2014, 22 (21), 6053. Shared first authorship.
  10. Durrant, J. D.; Votapka, L.; Sorensen, J.; Amaro, R. E. POVME 2.0: An Enhanced Tool for Determining Pocket Shape and Volume Characteristics. J. Chem. Theory Comput. 2014, 10 (11), 5047.
  11. Feher, V. A.; Durrant, J. D.; Van Wart, A. T.; Amaro, R. E. Computational approaches to mapping allosteric pathways. Curr. Opin. Struc. Biol. 2014, 25 98. Cover article.
  12. Van Wart, A. T.; Durrant, J. D.; Votapka, L.; Amaro, R. E. Weighted Implementation of Suboptimal Paths (WISP): An Optimized Algorithm and Tool for Dynamical Network Analysis. J. Chem. Theory Comput. 2014, 10 (2), 511. Shared first authorship.
  13. Durrant, J. D.; Amaro, R. E. WebChem Viewer: a tool for the easy dissemination of chemical and structural data sets. BMC Bioinf. 2014, 15, 159.
  14. Durrant, J. D.; Amaro, R. E. LipidWrapper: an algorithm for generating large-scale membrane models of arbitrary geometry. PLoS Comput. Biol. 2014, 10 (7), e1003720.
  15. Durrant, J. D.; Friedman, A. J.; Rogers, K. E.; McCammon, J. A. Comparing neural-network scoring functions and the state of the art: applications to common library screening. J. Chem. Inf. Model. 2013, 53 (7), 1726.
  16. Durrant, J. D.; Lindert, S.; McCammon, J. A. AutoGrow 3.0: An Improved Algorithm for Chemically Tractable, Semi-Automated Protein Inhibitor Design. J. Mol. Graphics Modell. 2013, 44, 104.
  17. Durrant, J. D.; Amaro, R. E. In De novo Molecular Design; Schneider, G., Ed.; Wiley-VCH: Weinheim, Germany, 2013.
  18. Rogers, K. E.; Keranen, H.; Durrant, J. D.; Ratnam, J.; Doak, A.; Arkin, M. R.; McCammon, J. A. Novel cruzain inhibitors for the treatment of Chagas’ disease. Chem. Biol. Drug Des. 2012, 80 (3), 398.
  19. Friedman, A. J.; Durrant, J. D.; Pierce, L. C. T.; McCorvie, T. J.; Timson, D. J.; McCammon, J. A. The Molecular Dynamics of Trypanosoma brucei UDP-Galactose 4 ‘-Epimerase: A Drug Target for African Sleeping Sickness. Chem. Biol. Drug Des. 2012, 80 (2), 173.
  20. Lindert, S.; Durrant, J. D.; McCammon, J. A. LigMerge: A Fast Algorithm to Generate Models of Novel Potential Ligands from Sets of Known Binders. Chem. Biol. Drug Des. 2012, 80 (3), 358.
  21. Durrant, J. D.; McCammon, J. A. AutoClickChem: Click Chemistry in Silico. PLoS Comput. Biol. 2012, 8 (3), e1002397.
  22. Durrant, J. D.; McCammon, J. A. Molecular dynamics simulations and drug discovery. BMC Biol. 2011, 9 71. “Highly accessed” article. Article recommended by the Faculty of 1000.
  23. Durrant, J. D.; Friedman, A. J.; McCammon, J. A. CrystalDock: a novel approach to fragment-based drug design. J. Chem. Inf. Model. 2011, 51 (10), 2573.
  24. Durrant, J. D.; McCammon, J. A. NNScore 2.0: A Neural-Network Receptor-Ligand Scoring Function. J. Chem. Inf. Model. 2011, 51 (11), 2897.
  25. Durrant, J. D.; McCammon, J. A. Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors. BMC Pharmacol. 2011, 11, 9.
  26. Durrant, J. D.; McCammon, J. A. HBonanza: A Computer Algorithm for Molecular-Dynamics-Trajectory Hydrogen-Bond Analysis. J. Mol. Graphics Modell. 2011, 31, 5.
  27. Durrant, J. D.; Cao, R.; Gorfe, A. A.; Zhu, W.; Li, J.; Sankovsky, A.; Oldfield, E.; McCammon, J. A. Non-Bisphosphonate Inhibitors of Isoprenoid Biosynthesis Identified via Computer-Aided Drug Design. Chem. Biol. Drug Des. 2011, 78 (3), 323. Shared first authorship. Cover article.
  28. Durrant, J. D.; Oliveira, C. d.; McCammon, J. A. Pyrone-Based Inhibitors of Metalloproteinases Types 2 and 3 May Work as Conformation-Selective Inhibitors. Chem. Biol. Drug Des. 2011, 78 (2), 191. Cover article.
  29. Durrant, J. D.; McCammon, J. A. BINANA: A novel algorithm for ligand-binding characterization. J. Mol. Graphics Modell. 2011, 29 (6), 888.
  30. Durrant, J. D.; de Oliveira, C. A.; McCammon, J. A. POVME: An algorithm for measuring binding-pocket volumes. J. Mol. Graphics Modell. 2011, 29 (5), 773.
  31. Sinko, W.; de Oliveira, C.; Williams, S.; Van Wynsberghe, A.; Durrant, J. D.; Cao, R.; Oldfield, E.; McCammon, J. A. Applying Molecular Dynamics Simulations to Identify Rarely Sampled Ligand-bound Conformational States of Undecaprenyl Pyrophosphate Synthase, an Antibacterial Target. Chem. Biol. Drug Des. 2011, 77 (6), 412. Article recommended by the Faculty of 1000.
  32. Durrant, J. D.; McCammon, J. A. Computer-aided drug-discovery techniques that account for receptor flexibility Curr. Opin. Pharmacol. 2010, 10 (6), 770.
  33. Durrant, J. D.; McCammon, J. A. NNScore: A Neural-Network-Based Scoring Function for the Characterization of Protein-Ligand Complexes. J. Chem. Inf. Model. 2010, 50 (10), 1865.
  34. Durrant, J. D.; Hall, L.; Swift, R. V.; Landon, M.; Schnaufer, A.; Amaro, R. E. Novel Naphthalene-Based Inhibitors of Trypanosoma brucei RNA Editing Ligase 1. PLoS Neglected Trop. Dis. 2010, 4 (8), e803.
  35. Durrant, J. D.; Urbaniak, M. D.; Ferguson, M. A.; McCammon, J. A. Computer-Aided Identification of Trypanosoma brucei Uridine Diphosphate Galactose 4′-Epimerase Inhibitors: Toward the Development of Novel Therapies for African Sleeping Sickness. J. Med. Chem. 2010, 53 (13), 5025.
  36. Durrant, J. D.; McCammon, J. A. Potential drug-like inhibitors of Group 1 influenza neuraminidase identified through computer-aided drug design. Comput. Biol. Chem. 2010, 34 (2), 97.
  37. Durrant, J. D.; Keranen, H.; Wilson, B. A.; McCammon, J. A. Computational identification of uncharacterized cruzain binding sites. PLoS Neglected Trop. Dis. 2010, 4 (5), e676. Shared first authorship.
  38. Durrant, J. D.; Amaro, R. E.; Xie, L.; Urbaniak, M. D.; Ferguson, M. A.; Haapalainen, A.; Chen, Z.; Di Guilmi, A. M.; Wunder, F.; Bourne, P. E.; McCammon, J. A. A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology. PLoS Comput. Biol. 2010, 6 (1), e1000648.
  39. Durrant, J. D.; de Oliveira, C. A. F.; McCammon, J. A. Including receptor flexibility and induced fit effects into the design of MMP-2 inhibitors. J. Mol. Recognit. 2010, 23 (2), 173.
  40. Swift, R. V.; Durrant, J.; Amaro, R. E.; McCammon, J. A. Toward understanding the conformational dynamics of RNA ligation. Biochemistry 2009, 48 (4), 709. Shared first authorship.
  41. Durrant, J. D.; Amaro, R. E.; McCammon, J. A. AutoGrow: A Novel Algorithm for Protein Inhibitor Design. Chem. Biol. Drug Des. 2009, 73 (2), 168.
  42. Durrant, J. D.; Caywood, D.; Busath, D. D. Tryptophan contributions to the empirical free-energy profile in gramicidin A/M heterodimer channels. Biophys. J. 2006, 91 (9), 3230.
  43. Durrant, J. D.; Gardunia, B. W.; Livingstone, K. D.; Stevens, M. R.; Jellen, E. N. An algorithm for analyzing linkages affected by heterozygous translocations: QuadMap. J. Hered. 2006, 97 (1), 62.
  44. Duffin, R. L.; Garrett, M. P.; Thompson, K. B.; Durrant, J. D.; Busath, D. D. Modulation of lipid bilayer interfacial dipole potential by phloretin, RH421, and 6-ketocholestanol as probed by gramicidin channel conductance. Langmuir 2003, 19 (4), 1439.
  45. Jellen, E. N.; Gardunia, B. W.; Durrant, J. D.; Raymond, F. D.; Murphy, J. P.; Livingston, D. P.; Santos, A. G. In American Oat Workers Conference Proceedings 2002.

Recent Invited Seminars and Presentations

DateInstitutionDescription
1/22/2016San Diego State UniversityAn invited seminar describing computer-aided drug design and large-scale model building.

Outreach Activities

  1. Served on the UCSD MSTP (MD/PhD) admissions committee for two years.
  2. Peer reviewed articles for Chemical Biology & Drug Design, Future Medicinal Chemistry, Molecular Informatics, and the Journal of Chemical Information and Modeling.
  3. Taught lectures in middle schools as part of the Salk Mobile Lab.

Provisional Patents

DateDescription
5/17/2011Novel inhibitors of farnesyl diphosphate synthase (FPPS) and undecaprenyl pyrophosphate synthase (UPPS) (61/487,222)
6/1/2010Novel inhibitors of Trypansoma brucei UDP-Galactose 4′-Epimerase (TbGaIE) (61/350,437)
4/26/2012Novel Inhibitors of the Trypanosoma cruzi Cysteine Protease Cruzain (61/639,038)
9/12/2012Potential African Sleeping Sickness Drugs (61/700,244)
2015Small Molecules to Reactivate the P53 Y220C Mutant (licensed, provisional patent to be filed soon)

In the Press

  1. Real Science Using Stampede’s Xeon Phi. Jorge Salazar, Texas Advanced Computing Center Press Release. 12/16/2014.
  2. New Models for Powerful Flu Fighters From Existing Drugs. Tina Hesman Saey, U.S. News and World Report. 12/9/2009.
  3. Breakthrough Flu Drug Might Already Exist. Lauren Gravitz, Technology Review (MIT). 12/8/2009
  4. Blessings Live in Brazil. Kate Evans, The Daily Universe (BYU). 3/8/2005.
  5. BYU Student to Graduate with Double Major and Master’s Degree, 4.0 GPA in five years. Lexi Allen, BYU News. 4/18/2005
  6. He’s a Triple-Threat Guy: BYU Student will Pick up Three Degrees. Todd Hollingshead, The Salt Lake Tribune. 04/21/2005.
  7. Serve Others, BYU Graduates Told. Laura Hancock, Deseret Morning News. 4/22/2005.
  8. Featured on Utah’s KUTV news.

Languages

Speaking Fluency: English, Portuguese, Spanish (limited)
Reading Fluency: English, Portuguese, Spanish


References

Prof. J. Andrew McCammon
HHMI, National Academy of Sciences, Department of Chemistry and Biochemistry
University of California San Diego
9500 Gilman Drive
La Jolla, CA 92093
Phone (858) 534-2905
Fax (858) 534-4974
jmccammon@nullmail.ucsd.edu

Prof. Rommie E. Amaro
Department of Chemistry and Biochemistry
University of California San Diego
9500 Gilman Drive
La Jolla, CA 92093
(858) 534-9629
ramaro@nullucsd.edu

Prof. Martin J. O’Donnell
Department of Chemistry & Chemical Biology
Indiana University-Purdue University Indianapolis
420 University Blvd
Indianapolis, IN 46202
(317) 274-6887
modonnel@nulliupui.edu