Structure, thermodynamics, dynamics, and assembly of macromolecules at complex aqueous interfaces

Abstract

Aqueous interfaces are ubiquitous and play an important role in many chemical and biological processes. Interfaces provide an inhomogeneous environment which affects the structure, dynamics, and interactions of molecules in their vicinity. In this work, we focus on the effects of chemical and topographical heterogeneities on the behavior of water and on water-mediated interactions between molecules near interfaces with increasing complexity, from simple flat self-assembled monolayers to complex and realistic biomolecules.

We extend our research to understand the behavior of water near chemically and topographically complex proteins surfaces. Specifically, we develop a new method based on a gradual drying of the protein hydration shell (using an external potential) to characterize the hydrophobicity of the surface at the nanoscale. Our method is motivated by 'density fluctuations-based' mapping of protein hydrophobicity, but is far more effective and efficient than previous methods. In combination with homology modeling of protein structures and molecular dynamics simulations, we apply the new method to characterize several biological systems -- the protein hydrophobin II and engineered antibodies associated with the Alzheimer's disease. Using the nanoscale characterization of these molecules and their mutants, we obtain insights into their interactions with other molecules and to surfaces. In addition to serving as a practical bridge to fundamental statistical mechanical ideas in the liquid state theory, our method and its applications may help better understand protein-ligand binding, protein aggregation, the rational design of bio-sensing devices and antibody-based drugs.

First, we study flexible molecules near flat solid surfaces in water. We show that hydrophobic-hydrophilic striped patterns on flat self-assembled monolayers can dramatically affect the conformations -- globular vs flat -- and dynamics -- isotropic vs directional -- of a flexible hydrophobic polymer near the surfaces. Our results not only highlight the lengthscale-dependent association behavior of hydrophobic motifs, but can also be employed to design nanoscopic mazes and other structures with potential applications from separations to sensors. Second, we study rigid patterned molecules -- buckyballs -- near a soft vapor-liquid interface of water. We show that water-mediated interactions between buckyballs are quantitatively and qualitatively different at the interface compared to that in the bulk. The differences suggest a catalytic role for soft aqueous interfaces in particle aggregation and self-assembly.