(334c) Combining Simulation and Spectroscopy to Determine the Structure and Orientation of a Carbohydrate Binding Module (CBM)-Inspired Model Peptide on Cellulose

Interfacial processes, such as the enzymatic conversion of
an insoluble polysaccharide at the solid-liquid interface, are critically important
to the design of new systems to convert renewable resources into green fuels
and chemicals. Despite this fact, we often lack a molecularly detailed understanding
of these interfaces that hinders the rational design of new and/or improved
biocatalytic systems. Atomistic simulations of biomolecular adsorption using
state-of-the-art multiscale molecular modeling tools have strong potential to
combine with advanced, surface-specific spectroscopy to elucidate structural
and mechanistic details at the interface. To this end, enhanced sampling methods
based on the metadynamics family of methods have been combined with
experimental data from sum frequency generation spectroscopy (SFG) to probe the
equilibrium structure(s) and preferred orientation(s) of a 14-residue peptide
fragment inspired by the carbohydrate binding module (CBM) of a cellulase. Experimental
SFG data indicates the CBM fragment adsorbs to the cellulose surface and aligns
along the fibers in a distinct orientation/conformation. We use a variety of molecular
simulations to provide molecular level insight to this observation and add
additional detail beyond the amide I backbone spectra, thus providing new
mechanistic insights regarding biomass conversion. Additionally, simulation
results are used to determine the energetic penalties for binding in alternate
orientations, and to identify the specific reasons for the observed behaviors. In
a broader sense, this integrated approach of combining computational methods
with experiments aims to determine the role of the surface in modulating
biomolecular structure, thereby permitting the rational design of new
biocatalytic approaches.