Paul Langan

Position: Associate Laboratory Director

Facility: High Flux Isotope Reactor, Spallation Neutron Source

Phone: (865) 241-1499

Paul Langan is the Associate Laboratory Director for Neutron Sciences at Oak Ridge National Laboratory, a joint faculty professor of Cellular and Molecular Biology at the University of Tennessee, a prestige research professor of Chemistry at the Toledo University, and he is Director of the DOE funded Center for Structural Molecular Biology (CSMB). He leads (Principle Investigator, PI) a National Institutes of Health (NIH) funded consortium that develops computational tools for neutron crystallography, and he has been involved in leading various ORNL and LANL LDRD funded projects over the years. In particular, he has led efforts to develop drugs against cancer and AIDS, to re-engineer enzymes, and to revolutionize the efficiency of cellulosic biomass conversion to fuels and other products. He is past Director of the DOE funded Protein Crystallography Station (PCS) at LANL, the lead for a University of California funded program led by San Diego on the cellular function of protein kinases. He is co-PI for several current DOE and NIH funded grants that are based on applying the techniques of imaging and crystallography. Other positions include the editorial board of the journal Cellulose, co-Editor for Acta Crystallographica Section D, chairman of the neutron scattering commission of the International Union of Crystallography (IUCr), member of the the IUCr Commission on Journals, past chairman of the neutron scattering group of the American Crystallographic Association (ACA), and chairman of the fiber diffraction interest group of the ACA.

After receiving a BSc in Physics from Edinburgh University, Paul was awarded a PhD in Biophysics from Keele University in 1990 and was then appointed to consecutive research fellowships by Keele University to develop neutron diffraction for biology at the Rutherford Appleton laboratory in Oxford. In 1994 Paul moved to the Institute Laue Langevin (ILL), Grenoble, where he was crystallography beam-line scientist and secretary for the ILL Biology College. In 1998 Paul moved to LANL to work on the design and construction of the PCS, for which he received a Distinguished Performance Award (2002). While at LANL Paul built and lead the proteomics and protein crystallography team in Bioscience Division, and directed a cross-directorate biofuels program that was instrumental in obtaining $50M in funding for the National Alliance for Advanced Biofuels (PI Jose Olivares). In April 2011 Paul moved to ORNL as a Senior Scientist and Distinguished Research and Development staff member to build science programs across associate directorates that exploit the world-leading neutron capabilities at ORNL, and to direct for the CSMB. After reorganization of the Neutron Science Directorate in October 2011 Paul became Director of the newly formed Biology and Soft Matter Division (BSMD). In this role Paul has established a culture of technical and scientific excellence, and partnership with other directorates to build strong multidisciplinary programs.

Education

BSc in Physics from Edinburgh University in 1985

PhD in Biophysics from Keele University in 1990

Research

Paul's research interests include the relationship between structure and function in biology and chemistry, new computational methods and instrumentation for crystallography and scattering, and building and leading multidisciplinary teams to address mission driven science in the areas of energy and the environment. He has published articles in the fields of biology, chemistry, physics, and material science and has a software copyright for a crystallography program called nCNS. His most recent impact has been in applying neutrons to study enzyme mechanism and drug binding, developing novel technologies and computational methods for neutron macromolecular crystallography, integrating neutron scattering with high performance computing, and in providing for the first time a detailed understanding of the cellulose and lignin components of cellulosic biomass.

Selected Publications

“Lignin Valorization in the Biorefinery” Arthur J. Ragauskas, Gregg T. Beckham, Mary J. Biddy, Richard Chandra, Fang Chen, Mark F. Davis, Brian H. Davison, Richard A. Dixon, Paul Gilna, Martin Keller, Paul Langan, Amit K. Naskar, Jack N. Saddler, Timothy J. Tschaplinski, Gerald A. Tuskan, Charles E. Wyman, Science, 16, 709, 2014.

"Neutron and ultrahigh resolution X-ray crystallography resolves the catalytic mechanism of dihydrofolate reductase" Qun Wan, Brad C. Bennett, Mark A Wilson, Andrii Kovalevsky, Paul Langan, Elizabeth E. Howell, Chris Dealwis, accepted to Proceedings of the National Academy of Sciences, 2014.

“Hydration Controls the Mechanical and Dynamical Properties of Cellulose” Loukas Petridis, Hugh O’Neill, Mariah Johnson, Bingxin Fan, Roland Schulz, Eugene Mamontov, Janna Maranas, Paul Langan and Jeremy C. Smith, accepted for Biochemistry, 2014.

“Combining X-ray and neutron crystallography with molecular simulation to study binding, isomerization, and epimerization of L-arabinose catalyzed by D-xylose isomerase” Paul Langan, Troy Wymore, Amandeep K. Sangha, Jerry M. Parks, Zamin Koo Yang, B. Leif Hanson, Zoe Fisher, Sax Mason, Matthew P. Blakeley, Trevor Forsyth, Jenny P. Glusker, H. L. Carrell, Jeremy C. Smith, David A. Keen, David E. Graham, and Andrey Kovalevsky, Structure, 22(9), 1287-1300,2014.

“Metal-free cAMP-dependent protein kinase can catalyze phosphoryl transfer” Gerlits, Oksana; Das, Amit; Keshwani, Malik; Taylor, Susan; Waltman, Mary Jo; Heller, William; Langan, Paul; Kovalevsky, Andrey, Biochemistry, 53, 3179-3186, 2014.

“Hydrolysis of DFP and the Nerve Agent (S)-Sarin by DFPase Proceeds Along Two Different Reaction Pathways: Implications for Engineering Bioscavengers” Troy Wymore, Martin J. Field, Paul Langan, Jeremy C. Smith and Jerry M. Parks, Journal of Physical Chemistry, 118 (17), 4479–4489, 2014.

“Engineering Acidic Streptomyces rubiginosus D-Xylose Isomerase by Rational Enzyme Design” Mary Jo Waltman, Zamin Koo Yang, Paul Langan, David Graham, Andrey Kovalevsky, Protein Engineering Design, 27. 59-64, 2014.

“Common Processes Driving the Thermochemical Pretreatment of Lignocellulosic Biomass” Paul Langan, Loukas Petridis, Hugh M. O’Neill, Sai Venkatesh Pingali, Marcus Foston, Yoshiharu Nishiyama, Roland Schulz, Benjamin Lindner, B. Leif Hanson, Shane Harton, William T. Heller, Volker Urban, Barbara R. Evans, S. Gnanakaran, Arthur J. Ragauskas, Jeremy C. Smith, Brian Davison, Green Chemistry, 16, 63-68, 2014.

”X-ray crystallographic studies of family 11 xylanase in complex with oligosaccharides: implications for the mechanism of retaining glycosidases” Qun Wan, Andri Kovalevsky, Qiu Zhang, Scott Hamilton-Brehm, Kevin Weiss, Marat Mustyakimov, Paul Langan, David Graham, Leighton Coates, Acta Cryst. D70, 11-23, 2014.

“Seeing the Chemistry in Biology with Neutron Crystallography” Julian Chen and Paul Langan, Physical Chemistry Chemical Physics 15, 13705-13712, 2013.

“Can neutrons aid in drug design? A joint X-ray/neutron crystallographic study of the HIV-1 protease in complex with clinical inhibitor amprenavir” Irene T. Weber, Mary Jo Waltman, Marat Mustyakimov, Matthew Blakeley, David A. Keen, Paul Langan, and Andrey Kovalevsky, Journal of Medicinal Chemistry, 56 (13), 5631–5635 2013.

”Insights into the phosphoryl transfer catalyzed by cAMP dependent protein kinase: An X-ray crystallographic study of complexes with various metals and peptide substrate SP20”, Oksana O. Gerlits, Mary Jo Waltman, Susan S. Taylor, Paul Langan, and Andrey Y. Kovalevsky, Biochemistry, 52, 3721-3727, 2013.

“Inhibition of D-xylose isomerase by polyols: atomic details by joint X-ray/neutron crystallography.” Andrey Kovalevsky, Leif Hanson, Sax Mason, Trevor Forsyth, S. Zoë Fisher, Marat Mustyakimov, David A. Keen, Paul Langan, Acta Crystallographica, D68, 1201-1206, 2012.

“Direct observation of hydrogen atom dynamics and interactions by ultra-high resolution neutron protein crystallographyAnisotropic dynamics of hydrogen atoms in proteins revealed by ultra-high resolution neutron crystallography” Julian C.-H. Chen, Zoe Fisher, B. Leif Hanson, Paul Langan, Andrey Y. Kovalevsky, PNAS, 109:15301-15306, 2012.

“A coarse-grained model for synergistic action of multiple enzymes on cellulose” Andrea Asztalos, Marcus Daniels, Anurag Sethi, Tongye Shen, Paul Langan, Antonio Redondo and S. Gnanakaran, Biotechnology for Biofuels, 5:55, 2012.

“Evidence for Complex Molecular Architectures for Solvent-Extracted Lignins” Shane E. Harton, Sai Venkatesh Pingali, Grady A. Nunnery, Darren Baker, S. Hunter Walker, David C. Muddiman, Tadanori Koga, Volker S. Urban, Paul Langan, ACS Macro Letters, 1, 568−573, 2012.

“Low and Room Temperature X-ray Structures of Protein Kinase A Ternary Complexes Shed New Light on Its Activity” Andrey Kovalevsky, Hanna Johnson, Leif Hanson, Mary Jo Waltman, Zoe Fisher, Susan Taylor and Paul Langan, Acta Crystallographica Section D68, 854-860, 2012.

“Neutron structure of human carbonic anhydrase II: A hydrogen bonded network “switch” is observed between pH 7.8 and 10.0” S.Z. Fisher, A.Y. Kovalevsky, M. Mustyakimov, D.N. Silverman, R. McKenna, P. Langan, Biochemistry, 50, 9421-9423, 2011.

“Restructuring crystalline cellulose hydrogen bond network enhances its depolymerization rate” Shishir P.S. Chundawat, Giovanni Bellesia, Nirman P. Uppugundla, Leonardo da Costa Sousa, Dahai Gao; Albert Cheh, Umesh Agarwal, Christopher M. Bianchetti, George N. Phillips Jr., Paul Langan, Venkatesh Balan, S. Gnanakaran, Bruce Dale, Journal of the American Chemical Society, 133, 11163-11174, 2011.

“Ionic liquid induced changes in cellulose structure associated with enhanced biomass hydrolysis” Samayan, I.P., Hanson, B., Langan, P., Schall, C. Biomacromolecules, 12, 3091-3098, 2011.

“Exploring new strategies for cellulosic biofuels production” P. Langan, S. Gnanakaran, K. D. Rector, N. Pawley, D. Fox, Dae Won Cho, and K. E. Hammel, Energy & Environmental Science, 4, 3820–3833, 2011.

“The elusive hydronium ion is found in an enzyme exchanging roles with a proton at lower pH” A. Y. Kovalevsky, B. L. Hanson, S. A. Mason, T. Yoshida, S. Z. Fisher, M. Mustyakimov, V. T. Forsyth, M. P. Blakeley, D. A. Keen, P. Langan, Angewande Chemie, 50, 7520-7523, 2011.

“High resolution neutron crystallographic studies of the hydration of coenzyme cob(II)alamin” Gerwald Jogl, Xiaoping Wang, Sax A. Mason, Andrey Kovalevsky, Marat Mustyakimov, Zoe Fisher, Christina Hoffman, Christoph Kratky, Paul Langan, Acta Crystallographica D67, 584-591, 2011.

“Regioselectivity of Enzymatic and Photochemical Single Electron Transfer Promoted Carbon-Carbon BondFragmentation Reactions of Tetrameric Lignin Model Compounds” Dae Won Cho, John A. Latham, Hea Jung Park, Paul Langan, Ung Chan Yoon, Debra Dunaway-Mariano, Patrick S. Mariano, Journal of Organic Chemistry, 76, 2840-2852, 2011

“Reintroducing electrostatics into Macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration” Tim Fenn; Michael Schnieders, Marat Mustyakimov; Chunjie Hu; Paul Langan; Vijay Pande; Axel Brunger, Structure, 19, 523-533, 2011.

“Reversible swelling of the cell wall of poplar biomass by ionic liquid at room temperature” M. Lucas, G.L. Wagner, Y. Nishiyama, L. Hanson, I. P.Samayam, C.A. Schall, P. Langan, K.D. Rector, Bioresource technology, 102, 4518-4523, 2011.

“Opportunities and challenges with the growth of neutron crystallography” P. Adams, P. Langan. Acta Cryst. D66, 1121-1123, 2010.

“Macromolecular Neutron Crystallography at the Protein Crystallography Station” A. Kovalevsky, Z.S. Fisher, H. Johnson, M. Mustyakimov, M.J. Waltman, P. Langan, Acta Cryst. D66, 1206-1212, 2010.

“Looking at hydrogen bonds in cellulose” Y. Nishiyama, P. Langan, M. Wada, T. Forsyth. Acta Cryst. D66, 1172-1177, 2010.

“In Silico studies of crystalline cellulose and its degradation by enzymes” G. Bellesia, A. Asztalos, T. Shen, P. Langan, A. Redondo, S. Gnanakaran, Acta Cryst. D66, 1184-1188, 2010.

“Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyze the quaternary state of oxidized hemoglobins” T. Mueser, W. Griffith, A. Kovalevsky, J. Guo, S. Seaver, P. Langan, L. Hanson Acta Cryst. D66, 1249-1256, 2010.

“Neutron structure and mechanistic studies of diisopropyl fluorphosphatase (DFPase)” J. Chen, M. Mustyakimov, B.P. Schoenborn, P. Langan, M.M. Blum, Acta Cryst. D66, 1131-1138, 2010.

“Enzymes for carbon sequestration: Neutron crystallographic studies of carbonic anhydrase” S.Z. Fisher, A.Y. Kovalevsky, J. Domsic, M. Mustyakimov, D.N. Silverman, R. McKenna, P. Langan, Acta Cryst. D66, 1178-1183, 2010.

“Using Neutron Protein Crystallography to Understand Enzyme Mechanisms.” J.P. Glusker, A.Y. Kovalevsky, L. Hanson, S. Z. Fisher, M. Mustyakimov, S. Mason, T. Forsyth, and P. Langan, Acta Cryst. D66, 1257-1261, 2010.

“Protonation states of histidine and other key residues in deoxy-human normal adult hemoglobin by neutron protein crystallography” Kovalevsky, Chatake, Shibayama, Park, Ishikawa,Mustyakimov, Fisher, Langan, Morimoto. Acta Cryst. D66, 1144-1152, 2010.

"The Nature and Kinetic Analysis of Carbon-Carbon Bond Fragmentation Reactions of Cation Radicals Derived from SET-Oxidation of Lignin Model Compounds" Mariano, Patrick; Cho, Daewon; Gnanakaran, S; Langan, Paul; Dunaway-Mariano, Debra; Yoon, Ung Chan; Pimentel, Adam; Maestas, Gabriel; Park, Heajung; Parthasarathi, Ramakrishnan, Journal of Organic Chemistry, 75, 6549-6562, 2010.

“Metal ion roles and the movement of hydrogen during reaction catalyzed by D-Xylose Isomerase: a joint X-ray and neutron diffraction study” Kovalevsky, A., Hanson, B.L., Fisher, S.Z., Mason, S.A., Forsyth, V.T., Mustyakimov, M., Blakeley, M. Kean, D., Glusker, J., Langan, P. Structure, 18:688-699, 2010.

“Role of protein dynamics in proton transfer: a joint X-ray and neutron study of amicyanin” Sukumar, Matthews, Langan, Davidson, Proc. Nat. Acad. Sci. USA, 107, 6817-6822, 2010.

“Protonation States of Potential Bohr Groups in the Time-of-Flight Neutron Structure of Human deoxy-Hemoglobin” Kovalevsky, A., Chatake, T., Ishiwawa, T., Shibayama, N., Park, S.-Y., Mustyakimov, M., Fisher, S.Z., Langan, P., Morimoto, Y. J. Mol. Biol., 398, 276-291 2010.

“The neutron structure of human carbonic anhydrase II: Implications for proton transfer.” Fisher, Kovalevsky, Mustyakimov, McKenna, Silverman, Langan, Biochemistry, 49:415-421 2010.

"Joint X-ray and neutron refinement with phenix.refine” Afonine, Pavel V.; Mustyakimov, Marat; Grosse-Kunstleve, Ralf W. N.W. Moriarty, Langan, P., Adams PD, Acta Cryst. D66: 1153-1163, 2010

"Conformational Flexibility of Soluble Cellulose Oligomers: Chain Length and Temperature Dependence" Shen, T., Langan, P., French, A.P., Johnson, G.P., Gnanakaran, S. J. Am. Chem. Soc. 131:14786-14794, 2009.

"Generalized X-ray and neutron crystallographic analysis: more accurate and complete structures of biological macromolecules" Adams, P.A., Mustyakimov, M., Afonine, P.V., Langan, P. Acta Cryst. D65, 567-573, 2009.

"Rapid determination of hydrogen positions and protonation states of diisopropyl fluorophosphatase (DFPase) by joint neutron and X-ray diffraction refinement" Marc-Michael Blum, Marat Mustyakimov, Heinz Rüterjans, Benno Schoenborn, Paul Langan, Julian C.-H. Chen, Proc. Nat. Acad. Sci., USA, 106(3), 713-718, 2009.

"Structure of the ternary MTX/NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design" Brad C Bennett; Qun Wan; Md Faiz Ahmad; Paul Langan, Chris Dealwis, Journal of Structural Biology, 166, 162-171, 2009.

"Neutron Protein Crystallography: Opportunities, challenges and limitations" Blakeley, M., Langan, P., Niimura, N., Podjarny, A. Current Opinion in Structural Biology, 18: 593-600, 2008.

"Hydrogen location in stages of an enzyme-catalyzed reaction: time-of-flight neutron structure of D-xylose isomerase with bound D-xylulose" Kovalevsky, A.Y., Katz, A.K., Carrell, H.L., Hanson, L., Mustyakimov, M., Fisher, S.Z., Coates, L., Schoenborn, B.P., Bunick, G.J., Glusker, J.P., Langan, P. Biochemistry (Rapid Reports) 47, 7595-7597, 2008.

"Neutron and X-ray structural studies of short hydrogen bonds in photoactive yellow protein" S.Z. Fisher, S. Anderson, R. Henning, K. Moffat, P. Langan, P. Thiyagarajan, Schultz, A.J. Acta Cryst D 63, 1178-1184, 2007.

"The Effect of Deuteration on Protein Structure: A High Resolution Comparison of Hydrogenated and Perdeuterated Haloalkane Dehalogenase" Xuying Liu, Lief Hanson, Paul Langan and Ronald E. Viola, Acta Cryst D 63, 1000-1008,

"X-ray structure of ammonia cellulose I: new insights into the conversion of cellulose I to cellulose IIII" Wada, M.; Nishiyama, Y.; Langan, P. Macromolecule, 39, 2947-2952, 2006.

"Complementary neutron and ultrahigh X-ray diffraction studies of Escherichia coli Dihydrofolate reductase complexed with methotrexate." Bennett, B.; Langan, P.; Coates, L.; Mustyakimov, M.; Schoenborn, B.P.; Dealwis, C. PNAS, 103, 18493-18498, 2006.

"Location of the active-site hydrogen atoms enzymes: time-of-flight neutron diffraction" Katz, A.; Li, X.; Carrell, H.L.; Hanson, B.L.; Langan, P.; Coates, L.; Schoenborn, B.P.; Glusker, J.P.; Bunick, G.J. PNAS, 103, 8342-8346, 2006.

"X-ray structure of ammonia cellulose I: new insights into the conversion of cellulose I to cellulose IIII" Wada, M.; Nishiyama, Y.; Langan, P. Macromolecule, 39, 2947-2952, 2006.

"Design of the next generation neutron macromolecular diffractometer at the spallation neutron source." Schultz, A.J.; Thiyagarajan, P.; Hodges, J.P.; Rehm, C.; Myles, D.A.A.; Langan, P.; Mesecar, A.D. J. Appl. Cryst. 38, 964-974, 2005.

"Cellulose IIII Crystal Structure and Hydrogen Bonding by Synchrotron X-ray and Neutron Fiber Diffraction", Wada, M.; Chanzy, H.; Nishiyama, Y.; Langan, P; Macromolecules, 37, 8548-8555, 2004.

"Protein Crystallography with spallation neutrons: the user facility at los alamos national laboratory" Langan, P; Greene, G.; Schoenborn, B.P.; J. App. Cryst. 37, 24-31, 2004.

"Protein Crystallography with spallation neutrons: Collecting and processing wavelength-resolved Laue protein data" Langan, P.; Greene, G.; J. App. Cryst. 37, 253-257 2004

“The crystal structure and hydrogen bonding system in cellulose I from synchrotron X-ray and neutron fiber diffraction” Nishiyama, Y.; Sugiyama, J.; Chanzy, H.; Langan, P.; J. Am. Chem. Soc., 125, 14300-14306 2003.

“Periodic disordered regions in ramie cellulose microfibrils” Nishiyama; Kim; Katsumata; May; Langan, Biomacromolecules, 4, 1013-1017, 2003.

"The crystal structure and hydrogen bonding system in cellulose I from synchrotron X-ray and neutron fiber diffraction", Nishiyama, Y.; Chanzy, H.; Langan, P.; J. Am. Chem. Soc. 124, 31, 9074-9082, 2002.

"Structural Characterisation of crystals of alpha-glycine during anomalous electrical behaviour", Langan, P.; Mason, S.A.; Myles, D.A.; Schoenborn, B.P.; Acta Cryst. B 58, 728-733, 2002

"X-ray structure of mercerized cellulose II at 1Å resolution", Langan, P.; Nishiyama, Y.; Chanzy, H.; Biomacromolecules, Vol. 2, No. 2, 410-416, 2001.

“A low Temperature neutron diffraction study of Mn12 acetate.” Langan, P.; Robinson, R.; Brown, J.; Argyriou, D.; Hendrickson, D.; Christou, G.; Acta Cryst. C57, 909-910, 2001.

"A novel optical insertion device for removing the time tail from spallation neutron sources", Langan, P.; Daemon, L.; Schoeborn, B.P.; Proc. SPIE, 4509, 66, 2001.

“A revised structure and hydrogen bonding scheme in cellulose II from a neutron fibre diffraction analysis” Langan, P.; Nishiyama, Y.; Chanzy, H.; J. Am. Chem. Soc., Vol. 121, No. 43, 9940-9946, 1999.

"Need for neutron diffraction instruments" Langan, P. & Schoenborn, B.P., Science v286 (#5442), 1089 1999.

“Laue neutron diffraction studies of coenzyme cob(II)alamin”, Langan, P.; Jogl, G.; Lehmann, M.S.; Wilkinson, C.; Kratky, C.; Acta Cryst. D55, 51-59, 1999

“Indication of a phase transition in the C15 laves phase TaV2D1.8 at low temperature”, Kemali; Sun; Mercer; Fernandez; Ross; Langan, P; J. Material Science Letters, 17, 153-155, 1998

Awards, Honors and Memberships

· Top 10 Los Alamos National Laboratory 2010 Science & Technology Development List for “Gaining insight into more efficiently converting plant biomass into biofuels” · Certificate of Appreciation in Recognition of Outstanding Science and Contributions, August 2009, Associate Directorate for Chemistry, Life, and Earth Sciences, Los Alamos National Laboratory · Outstanding Performance and Lasting Contribution Award, August 2008, Bioscience Division, Los Alamos National Laboratory · Outstanding Employee Award, August 2005, Bioscience Division, Los Alamos National Laboratory · Distinguished Performance Award, August 2002, Los Alamos National Laboratory · Outstanding Achievement Award, August 2001, Bioscience Division, Los Alamos National Laboratory