Conversion of lignocellulose to biofuels is partly inefficient due to the deleterious impact of cellulose crystallinity on enzymatic saccharification. We demonstrate how the synergistic activity of cellulases was enhanced by altering the hydrogen bond network within crystalline cellulose fibrils. We provide a molecular-scale explanation of these phenomena through molecular dynamics (MD) simulations and enzymatic assays. Ammonia transformed the naturally occurring crystalline allomorph I(β) to III(I), which led to a decrease in the number of cellulose intrasheet hydrogen bonds and an increase in the number of intersheet hydrogen bonds. This rearrangement of the hydrogen bond network within cellulose III(I), which increased the number of solvent-exposed glucan chain hydrogen bonds with water by ~50%, was accompanied by enhanced saccharification rates by up to 5-fold (closest to amorphous cellulose) and 60-70% lower maximum surface-bound cellulase capacity. The enhancement in apparent cellulase activity was attributed to the "amorphous-like" nature of the cellulose III(I) fibril surface that facilitated easier glucan chain extraction. Unrestricted substrate accessibility to active-site clefts of certain endocellulase families further accelerated deconstruction of cellulose III(I). Structural and dynamical features of cellulose III(I), revealed by MD simulations, gave additional insights into the role of cellulose crystal structure on fibril surface hydration that influences interfacial enzyme binding. Subtle alterations within the cellulose hydrogen bond network provide an attractive way to enhance its deconstruction and offer unique insight into the nature of cellulose recalcitrance. This approach can lead to unconventional pathways for development of novel pretreatments and engineered cellulases for cost-effective biofuels production.

The effect of beta-sheet propensity on the structural features of peptide aggregates was investigated using an off-lattice coarse-grained peptide model. A phase diagram as a function of temperature and beta-sheet propensity reveals a diverse family of supramolecular assemblies. Highly rigid peptides (peptides with high beta-sheet propensity) are seen to assemble predominantly into fibrillar structures. Increasing the flexibility of the peptide (reducing beta-sheet propensity) leads to a variety of structures, including fibrils, beta-barrel structures, and amorphous aggregates. Nonfibrillar entities have been suggested as primary causative agents in amyloid diseases and our simulations indicate that mutations that decrease beta-sheet propensity will decrease fibril formation and favor the formation of such toxic oligomers. Parallels between beta-sheet aggregates and nematic liquid crystals are discussed.

In this quantum chemical study, we explore hydrogen bonding (H-bonding) and stacking interactions in different crystalline cellulose allomorphs; namely, cellulose I(β) and cellulose III(I). We consider a model system representing a cellulose crystalline core made from six cellobiose units arranged in three layers with two chains per layer. We calculate the contributions of intrasheet and intersheet interactions to the structure and stability in both cellulose I(β) and cellulose III(I) crystalline cores. Reference structures for this study were generated from molecular dynamics simulations of water-solvated cellulose I(β) and III(I) fibrils. A systematic analysis of various conformations describing different mutual orientations of cellobiose units is performed using the hybrid density functional theory with the M06-2X with 6-31+G(d,p) basis sets. We dissect the nature of the forces that stabilize the cellulose I(β) and cellulose III(I) crystalline cores and quantify the relative strength of H-bonding and stacking interactions. Our calculations demonstrate that individual H-bonding interactions are stronger in cellulose I(β) than in cellulose III(I); however, the total H-bonding contribution to stabilization is larger in cellulose III(I) because of the highly cooperative nature of the H-bonding network. In addition, we observe a significant contribution from cooperative stacking interactions to the stabilization of cellulose I(β). The theory of atoms-in-molecules (AIM) has been employed to characterize and quantify these intermolecular interactions. AIM analyses highlight the role of nonconventional CH···O H-bonding in the cellulose assemblies. Finally, we calculate molecular electrostatic potential maps for the cellulose allomorphs that capture the differences in chemical reactivity of the systems considered in our study.

The authors introduce a novel mid-resolution off-lattice coarse-grained model to investigate the self-assembly of beta-sheet forming peptides. The model retains most of the peptide backbone degrees of freedom as well as one interaction center describing the side chains. The peptide consists of a core of alternating hydrophobic and hydrophilic residues, capped by two oppositely charged residues. Nonbonded interactions are described by Lennard-Jones and Coulombic terms. The influence of different levels of "hydrophobic" and "steric" forces between the side chains of the peptides on the thermodynamics and kinetics of aggregation was investigated using Langevin dynamics. The model is simple enough to allow the simulation of systems consisting of hundreds of peptides, while remaining realistic enough to successfully lead to the formation of chiral, ordered beta tapes, ribbons, as well as higher order fibrillar aggregates.

The kinetics of peptide oligomerization was investigated using Langevin Dynamics simulations and a coarse-grained peptide model. The simulations show a rich diversity of aggregation pathways, modulated by the beta-sheet propensity (flexibility) of the peptide. Aggregation into amyloidlike fibrils occurs via three main mechanisms: (i) formation of fibrils directly from the assembly of early ordered oligomers, (ii) fibril formation via the formation of on-pathway, nonfibrillar aggregates high in beta-sheet content, and (iii) formation of amorphous aggregates followed by reorganization to beta-sheet aggregates and to fibrils. beta-sheet, nonfibrillar aggregates also appeared as long-lived, "off-pathway" end-product species.