Gregg T. Beckham
I am a staff engineer at the National Renewable Energy Laboratory's National Bioenergy Center. Detailed information about my research is provided below.
Ph.D., Chemical Engineering, Massachusetts Institute of Technology, 2002–2007
M.S., Chemical Engineering Practice, Massachusetts Institute of Technology, 2002–2004
B.S., Chemical Engineering, Oklahoma State University, 1998–2002
- Senior Engineer, National Renewable Energy Laboratory, National Bioenergy Center, 2011–present
- Staff Engineer, National Renewable Energy Laboratory, National Bioenergy Center, 2008–2011
- Research Assistant Professor, Department of Chemical Engineering, Colorado School of Mines, 2010–present
- Affiliate, Renewable and Sustainable Energy Institute, University of Colorado at Boulder, 2010–present
- Station Director, Massachusetts Institute of Technology, David H. Koch School of Chemical Engineering Practice, 2007
- Lecturer, Massachusetts Institute of Technology, Singapore-MIT Alliance, 2005
- Cellulase enzyme structure-function relationships
- Biopolymer material properties
- Catalyst design for lignin deconstruction and utilization
- Nucleation of model and natural systems
- Statistical mechanics methods
- MIT David H. Koch School of Chemical Engineering Practice at NREL
Cellulase Enzyme Structure-Function Relationships
I am interested in the mechanisms by which processive cellulase enzymes interact with and degrade crystalline cellulose with an aim to design enhanced cellulase systems as well as biomimetic chemical catalysts for overcoming biomass recalcitrance. To date, my research efforts have focused on the Family 7 cellobiohydrolase (Cel7A) from Trichoderma reesei, which is one of the primary components of industrial enzyme cocktails for biomass conversion.
We study the individual sub-domains of this particular enzyme. To date, we have predicted that the Cel7A CBM exhibits 1 nanometer potential energy wells along the hydrophobic cellulose surface, we have shown that the linker is an intrinsically disordered protein with and without glycosylation, and with Tina Jeoh at UC Davis we demonstrated that changes to glycosylation affects the enzyme activity substantially. We have additional computational and experimental studies in progress on this enzyme, and related cellulase and hemicellulase enzymes from fungal and bacterial systems. Our recent review articles in Current Opinion in Biotechnology and Annual Reviews in Chemical and Biomolecular Engineering describe the capabilities and limitations of molecular and coarse-grained simulation approaches to aid experimental studies to understand structure-function relationships in carbohydrate-active enzymes.
The simulation tools we used for this research include Transition Path Sampling, Aimless Shooting and Likelihood Maximization, Replica-Exchange Molecular Dynamics, and a suite of free energy methods such as MD Umbrella Sampling, Equilibrium Path Sampling, and the Finite Temperature String Method. Our group primarily uses CHARMM, Amber, LAMMPS, and NAMD, and two staff members at NREL are involved in the development of the first three codes mentioned (namely, Mike Crowley and Antti-Pekka Hynninen).
Biopolymer Material Properties
Cellulose and chitin are two of the most abundant biological materials on Earth, and both polymers form recalcitrant, crystalline matrices for defense and structure. Enzymes, such as the Cel7A cellulase shown above, have evolved to deconstruct cellulose and chitin to soluble carbohydrates, but because both polymers form crystalline bundles in nature, enzymes must conduct work to decrystallize individual polymers from crystal surfaces. The work that enzymes must conduct is a function of the particular crystal form, or polymorph, of the polymer of interest (cellulose and chitin both have multiple crystal forms), the location of the chain on the crystal surface, and the degree of crystallinity in the substrate. We have used free energy methods to calculate the amount of work that cellulases must conduct to decrystallize cellulose as a function of cellulose polymorph and location of chains on crystal surfaces, as shown below.
Recently, Christy Payne and I also examined decrystallization of cello-oligomers on the surface of cellulose Iβ. Overall, this body of work has shown that inter-sheet interactions in cellulose dominate the work that enzymes must conduct at short oligomer lengths, and that intra-sheet hydrogen bonds begin to contribute substantially to decrystallization free energy at longer oligomer lengths. We have also shown that the decrystallization work for cellulose II and IIII chains, which are produced via some ionic liquid and ammonia pretreatment strategies respectively, is substantially lower than that for equivalent chains in cellulose I, the latter which is found in plant cell walls.
I also recently extended this work to decrystallization of polymer chains from the hydrophobic face of α-chitin. We showed that the inter-sheet hydrogen bonds present in α-chitin are responsible for much of the work that chitinases must conduct to deconstruct chitin. We are currently extending this work to β-chitin, which is a popular substrate for examining chitinase activity.
Catalyst Design for Lignin Deconstruction and Utilization
Lignin is a heterogeneous, alkyl-aromatic polymer found in plant cell walls for defense, structure, and water transport. Lignin is composed of three types of phenyl propanoid monomer units, linked together by various carbon-carbon and carbon-oxygen bonds. An illustration of lignin is shown below. In current selective routes for biomass utilization, lignin is typically burned for heat and power. However, the energy and aromatic content in lignin makes it an attractive target for catalytic conversion to usable intermediates for fuels and chemicals. Our group is also interested in designing chemical and biological catalysts to deconstruct and upgrade lignin to value-added molecules.
We use a combined theoretical and experimental approach to understand the most labile bonds in lignin, to design catalysts to cleave those bonds, and to understand how various pretreatment options affect lignin structure and chemistry. The theoretical component of our work utilizes quantum mechanical calculations with transition state theory to understand reaction mechanisms, barrier heights, and rates with various homogeneous and heterogeneous catalysts from the literature and from our own designs. Experimentally, we have synthesized large libraries of model compounds to mimic the most prevalent linkages in lignin, which are used in catalyst screening. We are also developing new methods to monitor catalytic deconstruction of lignin coupled with advanced analytical techniques to characterize product distributions. This information will be used directly in techno-economic models to couple our laboratory-scale work to understanding how lignin utilization will be integrated into next-generation biorefineries.
Nucleation of Model and Natural Systems
I am also interested in quantitatively describing the mechanisms by which systems self-assemble into ordered phases from disordered phases with molecular simulation. We recently examined the reaction coordinate for nucleation in a common model system, the Lennard-Jones fluid, and verified the first accurate scalar reaction coordinate for nucleation in this system.
In collaboration with faculty from the Center for Hydrate Research at the Colorado School of Mines, we are examining the mechanisms by which water can structure around small molecules to nucleate and grow into crystalline phases, called clathrate hydrates. Clathrate hydrates are a potentially important energy source and route for carbon sequestration, and thus understanding how they form at the molecular level is of paramount importance for energy and climate security. Also, with Valeria Molinero at the University of Utah, we are examining nucleation pathways to form ice and hydrate clathrate structures with advanced sampling methods.
Statistical Mechanics Methods
In the laboratory of Bernhardt L. Trout at MIT and in collaboration with Baron Peters (now at UCSB), I was involved in the development and deployment of aimless shooting and likelihood maximization, which is a useful combination of methods to find reaction coordinates for rare events in complex systems.
The following files are available for download:
The code for aimless shooting in CHARMM and NAMD in an example system (the solid-solid polymorph transformation in terephthalic acid) is executed by a simple shell script that calls an MD engine and performs the bookkeeping tasks for accepting or rejecting trajectories.
The code for likelihood maximization was written by Baron Peters.
We are currently implementing aimless shooting and a related method to compute free energy, equilibrium path sampling, into CHARMM.
In addition, Baron and I recently wrote a book chapter describing the practical aspects of transition path sampling, aimless shooting, and likelihood maximization.
MIT David H. Koch School of Chemical Engineering Practice at NREL
I am also involved with deployment of the MIT Practice School within the National Bioenergy Center at NREL. As of August 2011, we have had four stations (a total of 33 students) of the David H. Koch School of Chemical Engineering Practice at MIT working on a variety of projects at NREL in the biochemical, thermochemical, and algal conversion platforms. Several peer-reviewed manuscripts resulting from these efforts are in preparation currently, and multiple presentations have been given at national conferences based on their work.
* Corresponding author
‡ Equally contributing author
M.G. Resch, B.S. Donohoe, J.O. Baker, S.R. Decker, E.A. Bayer, G.T. Beckham, M.E. Himmel. (2013). "Fungal Cellulases and Complexed Cellulosomal Enzymes Exhibit Synergistic Mechanisms in Cellulose Deconstruction." Energy Env. Sci. In press.
S.C. Chmely, S. Kim, P.N. Ciesielski, G. Jimenez-Oses, R.S. Paton,* G.T. Beckham.* (2013). "Mechanistic Study of a Ru-Xantphos Catalyst for Tandem Alcohol Dehydrogenation and Reductive Aryl-Ether Cleavage." ACS Catal. (3:5); pp. 963-974.
C.B. Taylor, C.M. Payne, M.E. Himmel, M.F. Crowley, C. McCabe,* G.T. Beckham.* (2013). "Binding Site Dynamics and Aromatic-Carbohydrate Interactions in Processive and Non-Processive Family 7 Glycoside Hydrolases." J. Phys. Chem. B. (117:17); pp. 4924-4933.
M. Wu, G.T. Beckham,* A.M. Larsson, T. Ishida, S. Kim, C.M. Payne, M.E. Himmel, M.F. Crowley, S.J. Horn, B. Westereng, K. Igarashi, M. Samejima, J. Ståhlberg, V.G.H. Eijsink, M. Sandgren.* (2013). "Crystal Structure and Computational Characterization of the Lytic Polysaccharide Monooxygenase GH61D from the Basidiomycota Fungus Phanerochaete chrysosporium." J. Biol. Chem. (288:18); pp. 12828-12839.
L. Bu,* M.F. Crowley, M.E. Himmel, G.T. Beckham.* (2013). "Computational Investigation of the pH Dependence of Loop Flexibility and Catalytic Function in Glycoside Hydrolases." J. Biol. Chem. (288:17); pp. 12175-12186.
M.H. Momeni, C.M. Payne, H. Hansson, N.E. Mikkelsen, J. Svedberg, Å. Engstrom, M. Sandgren, G.T. Beckham,* J. Ståhlberg.* (2013). "Structural, Biochemical, and Computational Characterization of the Glycoside Hydrolase Family 7 Cellobiohydrolase of the Tree-Killing Fungus Heterobasidion irregulare." J. Biol. Chem. (288:8); pp. 5861-5872.
P.K. GhattyVenkataKrishna, E.M. Alekozai, G.T. Beckham, R. Schulz, M.F. Crowley, E.C. Uberbacher, X. Cheng. (2013). "Initial Recognition of a Cellodextrin Chain in the Cellulose-Binding Tunnel May Affect Cellobiohydrolase Directional Specificity." Biophys. J. (104:4); pp. 904-912.
D.W. Sammond, C.M. Payne, R. Brunecky, M.E. Himmel, M.F. Crowley, G.T. Beckham.* (2012). "Cellulase Linkers are Optimized Based on Domain Type and Function: Insights from Sequence Analysis, Biophysical Measurements, and Molecular Simulation." PLOS ONE (7:11); e48615.
C.M. Payne, J. Baban, S.J. Horn, P.H. Backe, A.S. Arvai, B. Dalhus, M. Bjørås, V.G.H. Eijsink, M. Sørlie, G.T. Beckham,* G. Vaaje-Kolstad.* (2012). "Hallmarks of processivity in glycoside hydrolases from crystallographic and computational studies of the Serratia marcescens chitinases." J. Biol. Chem. (287:43); pp. 36322-36330.
L. Bu,* M.R. Nimlos, M.R. Shirts, J. Ståhlberg, M.E. Himmel, M.F. Crowley, G.T. Beckham.* (2012). "Product Binding Varies Dramatically between Processive and Nonprocessive Cellulase Enzymes." J. Biol. Chem. (287:29); pp. 24807-24813.
M.R. Nimlos, G.T. Beckham, J. F. Matthews, L. Bu, M.E. Himmel, M.F. Crowley. (2012). "Binding Preferences, Surface Attachment, Diffusivity, and Orientation of a Family 1 Carbohydrate-Binding Module on Cellulose." J. Biol. Chem. (287:24); pp. 20603-20612.
K.J. Vicari, S. Tallam, T. Shatova, K. Koh, C.J. Scarlata, D. Humbird, E.J. Wolfrum,* G.T. Beckham.* (2012). "Uncertainty in Techno-Economic Estimates of Cellulosic Ethanol Production due to Experimental Measurement Uncertainty." Biotech. Biofuels (5:23).
J.F. Matthews, G.T. Beckham, M. Bergenstråhle-Wohlert, J.W. Brady, M.E. Himmel, M.F. Crowley. (2012). "Comparison of Cellulose Iβ Simulations with Three Carbohydrate Force Fields." J. Chem. Theor. Comp. (8); pp. 735-748.
G.T. Beckham,* Z. Dai, J.F. Matthews, M. Momany, C.M. Payne, W.S. Adney, S.E. Baker, M.E. Himmel. (2012). "Harnessing Glycosylation to Improve Cellulase Activity." Curr. Opin. Biotech. (23:3); pp. 338-345.
C.B. Taylor, M.F. Talib, C. McCabe,* L. Bu, W.S. Adney, M.E. Himmel, M.F. Crowley, G.T. Beckham.* (2012). "Computational Investigation of Glycosylation Effects on a Family 1 Carbohydrate-Binding Module." J. Biol. Chem. (287:5); pp. 3147-3155.
C.M. Payne, Y.J. Bomble, C.B. Taylor, C. McCabe, M.E. Himmel, M.F Crowley, G.T. Beckham.* (2011). "Multiple Functions of Aromatic-Carbohydrate Interactions in a Processive Cellulase Examined with Molecular Simulation." J. Biol. Chem. (286:47); pp. 41028-41035.
M.R. Walsh, J.D. Rainey, P.G. Lafond, D.H. Park, G.T. Beckham, M.D. Jones, K.H. Lee, C.A. Koh, E.D. Sloan, D.T. Wu, A.K. Sum. (2011). "The Cages, Dynamics, and Structuring of Incipient Methane Clathrate Hydrates." Phys. Chem. Chem. Phys. (13); pp. 19951-19959.
S. Kim, S.C. Chmely, M.R. Nimlos, Y.J. Bomble, T.D. Foust, R.S. Paton, G.T. Beckham.* (2011). "Computational Study of Bond Dissociation Enthalpies for a Large Range of Native and Modified Lignins." J. Phys. Chem. Lett. (2); pp. 2846-2852.
M.R. Walsh, G.T. Beckham, C.A. Koh, E.D. Sloan, D.T. Wu, A.K. Sum. (2011). "Methane Hydrate Nucleation Rates from Molecular Dynamics Simulations: Effects of Aqueous Methane Concentration, Interfacial Curvature, and System Size." J. Phys. Chem. C. (115:43); pp. 21241-21248.
Y. Lin, J. Silvestre-Ryan, M.E. Himmel, M.F. Crowley, G.T. Beckham, J.W. Chu. (2011). "Protein Allostery at the Solid-Liquid Interface: Endoglucanase Attachment to Cellulose Affects Glucan Clenching in the Binding Cleft." J. Amer. Chem. Soc. (133:41); pp. 16617-16624.
A.P. Hynninen, J.F. Matthews, G.T. Beckham, M.F. Crowley, M.R Nimlos. (2011). "Coarse-Grain Model for Glucose, Cellobiose, and Cellotetraose in Water." J. Chem. Theor. Comp. (7); pp. 2137-2150.
C.M. Payne,* M.E. Himmel, M.F. Crowley, G.T. Beckham.* (2011). "Decrystallization of Oligosaccharides from the Cellulose Iβ Surface with Molecular Simulation." J. Phys. Chem. Lett. (2); pp. 1546-1550.
L. Bu, G.T. Beckham, M.R. Shirts, M.R. Nimlos, W.S. Adney, M.E. Himmel, M.F. Crowley. (2011). "Probing Carbohydrate Product Expulsion from a Processive Cellulase with Multiple Absolute Binding Free Energy Methods." J. Biol. Chem. (286:20); pp. 18161-18169.
G.T. Beckham,* B. Peters. (2011). "Optimizing Nucleus Size Metrics for Liquid–Solid Nucleation from Transition Paths of Near-Nanosecond Duration." J. Phys. Chem. Lett. (2); pp. 1133-1138.
G.T. Beckham,* M.F. Crowley. (2011). "Examination of the α-Chitin Structure and Decrystallization Thermodynamics at the Nanoscale." J. Phys. Chem. B (115:15); pp. 4516-4522.
G.T. Beckham,* J.F. Matthews, B. Peters, Y.J. Bomble, M.E. Himmel, M.F. Crowley.* (2011). "Molecular-Level Origins of Biomass Recalcitrance: Decrystallization Free Energies for Four Common Cellulose Polymorphs." J. Phys. Chem. B (115:14); pp. 4118-4127.
Y.J. Bomble, G.T. Beckham, J.F. Matthews, M.R. Nimlos, M.E. Himmel, M.F. Crowley. (2011). "Modeling the Self-Assembly of the Cellulosome Enzyme Complex." J. Biol. Chem. (286:7); pp. 5614-5623.
J.F. Matthews, M. Bergenstråhle, G.T. Beckham, M.E. Himmel, M.R. Nimlos, J.W. Brady, M.F. Crowley. (2011). "High-Temperature Behavior of Cellulose I." J. Phys. Chem. B. (115:10); pp. 2155-2166.
S.P.S. Chundawat,*‡ G.T. Beckham,*‡ M.E. Himmel, B.E. Dale. (2011). "Deconstruction of Lignocellulosic Biomass to Fuels and Chemicals." Ann. Rev. Chem. Biomolec. Eng. (2); pp. 121-145.
G.T. Beckham, Y.J. Bomble, E.A. Bayer, M.E. Himmel, M.F. Crowley. (2011). "Applications of Computational Science for Understanding Enzymatic Deconstruction of Cellulose." Curr. Opin. Biotech. (22:2); pp. 231-238.
G.T. Beckham,* Y.J. Bomble, J.F. Matthews, C.B. Taylor, M.G. Resch, J.M. Yarbrough, S.R. Decker, L. Bu, X. Zhao, C. McCabe, J. Wohlert, M. Bergenstråhle, J.W. Brady, W.S. Adney, M.E. Himmel, M.F. Crowley.* (2010). "The O-Glycosylated Linker from the Trichoderma reesei Family 7 Cellulase Is a Flexible, Disordered Protein." Biophysical J. (99:11); pp. 3773-3781.
G.T. Beckham,* J.F. Matthew, Y.J. Bomble, L. Bu, W.S. Adney, M.E. Himmel, M.R. Nimlos, M.F. Crowley.* (2010). "Identification of Amino Acids Responsible for Processivity for a Family 1 Carbohydrate-Binding Module from a Fungal Cellulase." J. Phys. Chem. B (114:3); pp. 1447-1453.
G.T. Beckham,* B. Peters. (2010). "New Methods to Find Accurate Reaction Coordinates from Path Sampling." Chapter 13. Nimlos, M., Crowley, M., eds. Computational Modeling in Lignocellulosic Biofuel Production, ACS Symposium Series, Vol. 1052, Washington, DC: American Chemical Society; pp. 299-332.
L. Bu,‡ G.T. Beckham,‡ M.F. Crowley, C.H. Chang, J.F. Matthews, Y.J. Bomble, W.S. Adney, M.E. Himmel, M.R. Nimlos. (2009). "The Energy Landscape for the Interaction of the Family 1 Carbohydrate-Binding Module and the Cellulose Surface is Altered by Hydrolyzed Glycosidic Linkages." J. Phys. Chem. B (113:31); pp. 10994-11002.
W.S. Adney, T. Jeoh, G.T. Beckham, Y-C. Chou, J.O. Baker, W. Michener, R. Brunecky, M.E. Himmel. (2009). "Probing the Role of N-linked Glycans in the Stability and Activity of Fungal Cellobiohydrolases by Mutational Analysis." Cellulose (16:4), pp. 699-709.
B. Peters, N.E.R. Zimmerman, G.T. Beckham, J.W. Tester, B.L. Trout. (2008). "Path Sampling Calculation of Methane Diffusivity in Natural Gas Hydrates from a Water-Vacancy Assisted Mechanism." J. Amer. Chem. Soc. (130:51); pp. 17342-17350.
G.T. Beckham, B. Peters, B.L. Trout. (2008). "Evidence for a Size Dependent Nucleation Mechanism in Solid State Polymorph Transformations." J. Phys. Chem. B (112:25); pp. 7460-7466.
B. Peters, G.T. Beckham, B.L. Trout. (2007). "Extensions to the Likelihood Maximization Approach." J. Chem. Phys., 127; 034109.
G.T. Beckham, B. Peters, C. Starbuck, N. Variankaval, B.L. Trout. (2007). "Surface-Mediated Nucleation in the Solid-State Polymorph Transformation of Terephthalic Acid." J. Amer. Chem. Soc. (129:15); pp. 4714-4723.
15013 Denver West Parkway, MS 3322
Golden, CO 80401
Email: Gregg Beckham
Phone: (303) 384-7806