Self-assembly of phenylalanine-based molecules.

Using molecular dynamics, we study the self-assembly of phenylalanine with charged end-groups at various temperatures and concentrations. As in the case of diphenylalanine, we observe the formation of nanotubes; however, phenylalanine aggregates in layers of four, not six, molecules. The observed aggregates are consistent with recent experimental measurements of fibrils obtained from mice with phenylketonuria. We investigate the stability and the mechanism by which these tubular structures form and discuss potential toxicity mechanisms.

Novel computational study on π-stacking to understand mechanistic interactions of Tryptanthrin analogues with DNA.

Based on recently published initial experimental results on the intercalation of a class of broad spectrum antiparasitic compounds, we present a purely theoretical approach for determining if these compounds may preferentially intercalate with guanosine/cytosine (GC)-rich or adenosine/thymidine (TA)-rich regions of DNA. The predictive model presented herein is based upon utilization of density functional theory (DFT) to determine a priori how the best intercalator may energetically and sterically interact with each of the nucleoside base pairs. A potential new method using electrostatic potential maps (EPMs) to visually select the best poses is introduced and compared to the existing brute-force center of mass (COM) approach. The EPM and COM predictions are in agreement with each other, but the EPM method is potentially much more efficient. We report that 4-azatryptantrin, the best intercalator, is predicted to favor π-stacking with GC over that of TA by approximately 2-4 kcal/mol. This represents a significant difference if one takes into account the Boltzmann distribution at physiological temperature. This theoretical method will be utilized to guide future experimental studies on the elucidation of possible mechanism(s) for the action of these antiparasitic compounds at the molecular level.