Interplay between human islet amyloid polypeptide aggregates and micro-heterogeneous membranes.

Human islet amyloid polypeptides (hIAPP) aggregate into amyloid deposits in the pancreatic islets of Langerhans, contributing to the loss of β-cells of patients with type 2 diabetes. Despite extensive studies of membrane disruption associated with hIAPP aggregates, the molecular details regarding the complex interplay between hIAPP aggregates and raft-containing membranes are still very limited. Using all-atom molecular dynamics simulations, we investigate the impact of hIAPP aggregate insertion on lipid segregation.

Approximating dynamic proximity with a hybrid geometry energy-based kernel for diffusion maps.

The diffusion map is a dimensionality reduction method. The reduction coordinates are associated with the leading eigenfunctions of the backward Fokker-Planck operator, providing a dynamic meaning for these coordinates. One of the key factors that affect the accuracy of diffusion map embedding is the dynamic measure implemented in the Gaussian kernel.

Observations on AMBER Force Field Performance under the Conditions of Low pH and High Salt Concentrations.

Molecular dynamics simulations have become an important tool for the study of structures, dynamics, and functions of biomolecules. Time scales and force field accuracy are key factors for the reliability of these simulations. With the advancement of computational platforms and simulation technologies, all-atom simulations of proteins in explicitly represented aqueous solutions can reach as long as milliseconds.

Long-Range Reactivity Modulations in Geranyl Chloride Derivatives.

Derivatives of geraniol are versatile synthetic intermediates that are useful for synthesizing a variety of terpenoid natural products; however, the results presented herein show that subtle differences in the structures of functionalized geranyl chlorides can significantly impact their abilities to function as effective electrophiles in synthetic reactions. A series of focused kinetics experiments identify specific structure-activity relationships that illustrate the importance not only of steric bulk, but also of electronic effects from distant regions of the molecules that contribute to their overall levels of reactivity. Computational modeling suggests that destabilization of the reactant by filled-filled orbital mixing events in some, but not all, conformations may be a critical contributor to these important electronic effects.