Christina L. Ting

A Kinetic Model for the Enzymatic Action of Cellulase

We develop a mechanochemical model for the dynamics of cellulase, a two-domain enzyme connected by a peptide linker, as it extracts and hydrolyzes a cellulose polymer from a crystalline substrate. We consider two random walkers, representing the catalytic domain (CD) and the carbohydrate binding module (CBM), whose rates for stepping are biased by the coupling through the linker and the energy required to lift the cellulose polymer from the crystalline surface. Our results show that the linker length and stiffness play a critical role in the cooperative action of the CD and CBM domains and that, for a given linker length, the steady-state hydrolysis shows a maximum at some intermediate linker stiffness. The maximum hydrolysis rate corresponds to a transition of the linker from a compressed to an extended conformation, where the system exhibits maximum fluctuation, as measured by the variance of the separation distance between the two domains and the dispersion around the mean hydrolysis speed. In the range of experimentally known values of the parameters of our model, improving the intrinsic hydrolytic activity of the CD leads to a proportional increase in the overall hydrolysis rate.

Two-dimensional fluorescence resonance energy transfer as a probe for protein folding: a theoretical study.

We describe a two-dimensional (2D), four-color fluorescence resonance energy transfer (FRET) scheme, in which the conformational dynamics of a protein is followed by simultaneously observing the FRET signal from two different donor-acceptor pairs. For a general class of models that assume Markovian conformational dynamics, we relate the properties of the emission correlation functions to the rates of elementary kinetic steps in the model. We further use a toy folding model that treats proteins as chains with breakable cross-links to examine the relationship between the cooperativity of folding and FRET data and to establish what additional information about the folding dynamics can be gleaned from 2D, as opposed to one-dimensional FRET experiments. We finally discuss the potential advantages of the four-color FRET over the three-color FRET technique.

Electrostatically Tuned Self-Assembly of Branched Amphiphilic Peptides

Electrostatics plays an important role in the self-assembly of amphiphilic peptides. To develop a molecular understanding of the role of the electrostatic interactions, we develop a coarse-grained model peptide and apply self-consistent field theory to investigate the peptide assembly into a variety of aggregate nanostructures. We find that the presence and distribution of charged groups on the hydrophilic branches of the peptide can modify the molecular configuration from extended to collapsed. This change in molecular configuration influences the packing into spherical micelles, cylindrical micelles (nanofibers), or planar bilayers. The effects of charge distribution therefore have important implications for the design and utility of functional materials based on peptides.

Membrane stress profiles from self-consistent field theory

Using self-consistent field theory (SCFT), we develop an accurate, local expression for the stress profiles in membranes and soft matter interfaces, in general. The bond stresses are expressed in terms of pre-computed chain propagators, which are used to describe the statistical weight of the molecules and therefore require minimal additional calculations. In addition, we overcome the resolution limit of the molecular bond length by including the Irving and Kirkwood bond assignment and recover a constant normal stress profile across an interface. Using this theory, we find that the membrane lateral stress profile contains repulsive (positive) stresses in the regions of the head and tail groups, and attractive (negative) stresses near the hydrophobic/hydrophilic interface. We also verify that the zeroth and first moments of the stress profile correspond to the thermodynamic tension and product of the bending modulus and the spontaneous curvature, respectively.