Ridgway Scott

Dehydron: A Structurally Encoded Signal for Protein Interaction

We introduce a quantifiable structural motif, called dehydron, that is shown to be central to protein-protein interactions. A dehydron is a defectively packed backbone hydrogen bond suggesting preformed monomeric structure whose Coulomb energy is highly sensitive to binding-induced water exclusion. Such preformed hydrogen bonds are effectively adhesive, since water removal from their vicinity contributes to their stability. At the structural level, a significant correlation is established between dehydrons and sites for protein complexation, with the HIV-1 capsid protein P24 complexed with antibody light-chain FAB25.3 providing the most dramatic correlation. Furthermore, the number of dehydrons in homologous similar-fold proteins from different species is shown to be a signature of proteomic complexity. The techniques are then applied to higher levels of organization: The formation of the capsid and its organization in picornaviruses correlates strongly with the distribution of dehydrons on the rim of the virus unit. Furthermore, antibody contacts and crystal contacts may be assigned to dehydrons still prevalent after the capsid has been assembled. The implications of the dehydron as an encoded signal in proteomics, bioinformatics, and inhibitor drug design are emphasized.

Continuum equations for dielectric response to macro-molecular assemblies at the nano scale

We study a frequency-dependent continuum model equation for electrostatics at the nano scale. It is motivated by the need to incorporate accurately the influence of dielectric correlations which are of the same length scale as the electrostatic fluctuations in protein?water systems. The model is based on a single parameter, a length scale for changes in the dielectric response, that is physically relevant. This parameter reflects the changes in the dielectric medium caused by local structuring of the molecules. We present three independent quantitative assessments of the model, including one in which the dielectric field is changing in time. The assessments involve modeling the local structuring of dielectrics around individual ions, explaining solvation of carbon nano-tube interiors and predicting accurately the electrostatic energy of ions in a carbon nano-tube. The latter involves comparing the frequency-dependent model equation directly with molecular dynamics simulations with explicit solvent. The model equation cannot be written as a differential equation but rather takes the form of a more general Fourier integral operator. It involves a non-local relationship between the polarization field and the electric field.

Bottom-up engineering of peptide cell translocators based on environmentally modulated quadrupole switches.

Designing water-soluble peptides that camouflage their polarity to cross an anhydrous phase may significantly impact drug delivery. We engineered neutrally charged peptides endowed with a conformational switch that enables them to solubilize in both water and lipid. These peptides are capable of translocating without resorting to active internalization mechanisms. Lipid solubility is induced by a quadrupolar arrangement. Our passive translocation motif possesses the highest efficiency and is derived from cellular prions.

C1 Continuity via Constraints for 4th Order Problems

Publisher Summary In this chapter, π represents a domain in the plane whose boundary consists of a finite number of non-intersecting polygonal arcs. The chapter explains a method for calculating the Ritz-Galerkin approximation from S n that views S n as a subspace of a larger space with explicit basis satisfying constraints. These constraints are not redundant because the matrix determining the Ritz-Galerkin approximation is invertible. The constraint method is studied in the engineering literature and is found to be competitive with other techniques.