[Show abstract][Hide abstract] ABSTRACT: Lignocellulosic biomass, a potentially important renewable organic source of energy and chemical feedstock, resists degradation to glucose in industrial hydrolysis processes and thus requires expensive thermochemical pretreatments. Understanding the mechanism of biomass breakdown during these pretreatments will lead to more efficient use of biomass. By combining multiple probes of structure, sensitive to different length scales, with molecular dynamics simulations, we reveal two fundamental processes responsible for the morphological changes in biomass during steam explosion pretreatment: cellulose dehydration and lignin-hemicellulose phase separation. We further show that the basic driving forces are the same in other leading thermochemical pretreatments, such as dilute acid pretreatment and ammonia fiber expansion.
Green Chemistry 01/2014; 16(1):63-68. · 6.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mercury (Hg) is a major global pollutant arising from both natural and anthropogenic sources. Defining the factors that determine the relative affinities of different ligands for the mercuric ion, Hg2+, is critical to understanding its speciation, transformation, and bioaccumulation in the environment. Here, we use quantum chemistry to dissect the relative binding free energies for a series of inorganic anion complexes of Hg2+. Comparison of Hg2+–ligand interactions in the gaseous and aqueous phases shows that differences in interactions with a few, local water molecules led to a clear periodic trend within the chalcogenide and halide groups and resulted in the well-known experimentally observed preference of Hg2+ for soft ligands such as thiols. Our approach establishes a basis for understanding Hg speciation in the biosphere.
[Show abstract][Hide abstract] ABSTRACT: Neutron scattering is a powerful technique that can be used to probe the structures and dynamics of complex systems. It can provide a fundamental understanding of the processes involved in the production of biofuels from lignocellulosic biomass. A variety of neutron scattering technologies are available to elucidate both the organization and deconstruction of this complex composite material and the associations and morphology of the component polymers and the enzymes acting on them, across multiple length scales ranging from Angstroms to micrometers and time scales from microseconds to picoseconds. Unlike most other experimental techniques, neutron scattering is uniquely sensitive to hydrogen (and its isotope deuterium), an atom abundantly present throughout biomass and a key effector in many biological, chemical, and industrial processes for producing biofuels. Sensitivity to hydrogen, the ability to replace hydrogen with deuterium to alter scattering levels, the fact that neutrons cause little or no direct radiation damage, and the ability of neutrons to exchange thermal energies with materials, provide neutron scattering technologies with unique capabilities for bioenergy research. Further, neutrons are highly penetrating, making it possible to employ sample environments that are not suitable for other techniques. The true power of neutron scattering is realized when it is combined with computer simulation and modeling and contrast variation techniques enabled through selective deuterium labeling.
[Show abstract][Hide abstract] ABSTRACT: Protein function often requires large-scale domain motion. An exciting new development in the experimental characterization of domain motions in proteins is the application of neutron spin-echo spectroscopy (NSE). NSE directly probes coherent (i.e., pair correlated) scattering on the ~1-100 ns timescale. Here, we report on all-atom molecular-dynamics (MD) simulation of a protein, phosphoglycerate kinase, from which we calculate small-angle neutron scattering (SANS) and NSE scattering properties. The simulation-derived and experimental-solution SANS results are in excellent agreement. The contributions of translational and rotational whole-molecule diffusion to the simulation-derived NSE and potential problems in their estimation are examined. Principal component analysis identifies types of domain motion that dominate the internal motion's contribution to the NSE signal, with the largest being classic hinge bending. The associated free-energy profiles are quasiharmonic and the frictional properties correspond to highly overdamped motion. The amplitudes of the motions derived by MD are smaller than those derived from the experimental analysis, and possible reasons for this difference are discussed. The MD results confirm that a significant component of the NSE arises from internal dynamics. They also demonstrate that the combination of NSE with MD is potentially useful for determining the forms, potentials of mean force, and time dependence of functional domain motions in proteins.
[Show abstract][Hide abstract] ABSTRACT: Nucleosome repositioning is a fundamental process in gene function. DNA elasticity is a key element of loop-mediated nucleosome repositioning. Two analytical models for DNA elasticity have been proposed: the linear sub-elastic chain (SEC), which allows DNA kinking, and the worm-like chain (WLC), with a harmonic bending potential. In vitro studies have shown that nucleosomes reposition in a discontiguous manner on a segment of DNA and this has also been found in ground-state calculations with the WLC analytical model. Here we study using Monte Carlo simulation the dynamics of DNA loop-mediated nucleosome repositioning at physiological temperatures using the SEC and WLC potentials. At thermal energies both models predict nearest-neighbor repositioning of nucleosomes on DNA, in contrast to the repositioning in jumps observed in experiments. This suggests a crucial role of DNA sequence in nucleosome repositioning.
[Show abstract][Hide abstract] ABSTRACT: The bacterial organomercurial lyase, MerB, catalyzes the protonolysis of organomercurial compounds. MerB cleaves Hg-C bonds of various substrates ranging from the methylmercury cation (MeHg) to merbromin. Upon Hg-C bond cleavage, Hg2+ and an organic molecule are produced. For example, methane is the product resulting from the protonolysis of MeHg. The release pathway and mechanism of the organic product are unclear. Here, we have applied molecular dynamics and free energy simulations to study the dissociation of a series of organic molecules. The x-ray crystallographic structure of MerB with a bound Hg2+ cation was used as the starting model, and the organic products were manually placed in the active site. The umbrella sampling method was used to obtain free energy profiles for the dissociation pathways. Several hydrophobic sidechains of MerB were found to interact with the organic molecules and may have important roles in the dissociation processes. The relatively low free energy barriers of dissociation suggest that organic product dissociation is not rate limiting.
[Show abstract][Hide abstract] ABSTRACT: A CHARMM molecular mechanics force field for lignin is derived. Parameterization is based on reproducing quantum mechanical data of model compounds. Partial atomic charges are derived by the examination of methoxybenzene: water interactions. Dihedral parameters are optimized by fitting to critical rotational potentials, and bonded parameters are obtained by optimizing vibrational frequencies and normal modes. The force field is validated by performing a molecular dynamics simulation of a crystal of a lignin fragment molecule and comparing simulation-derived structural features with experimental results. Together with the existing force field for polysaccharides, this work will enable full simulations of lignocellulose.
Journal of Physics Conference Series 08/2008; 125(1):012055.
[Show abstract][Hide abstract] ABSTRACT: Computer simulations have been performed to obtain an atomic-level understanding of lignocellulose structure and the assembly of its associated cellulosomal protein complexes. First, a CHARMM molecular mechanics force field for lignin is derived and validated by performing a molecular dynamics simulation of a crystal of a lignin fragment molecule and comparing simulation-derived structural features with experimental results. Together with the existing force field for polysaccharides, this work provides the basis for full simulations of lignocellulose. Second, the underlying molecular mechanism governing the assembly of various cellulosomal modules is investigated by performing a novel free-energy calculation of the cohesin-dockerin dissociation. Our calculation indicates a free-energy barrier of 17 kcal/mol and further reveals a stepwise dissociation pathway involving both the central -sheet interface and its adjacent solvent-exposed loop/turn regions clustered at both ends of the -barrel structure.