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Science still does not have the ability to accurately predict the affinity that ligands have for proteins. In an attempt to address this, the Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) series of blind predictive challenges is a community-wide exercise aimed at advancing computational techniques as standard predictive tools in rational drug design. In each cycle, a range of biologically relevant systems of different levels of complexity are selected to test the latest modeling methods. As part of this on-going exercise, and as a step towards understanding the important factors in context dependent guest binding, we challenged the computational community to determine the affinity of a series of negatively and positively charged guests to two constitutionally isomeric cavitand hosts: octa-acid 1 , and exo -octa acid 2 . Our affinity determinations, combined with molecular dynamics simulations, reveal asymmetries in affinities between host–guest pairs that cannot alone be explained by simple coulombic interactions, but also point to the importance of host–water interactions. Our work reveals the key facets of molecular recognition in water, emphasizes where improvements need to be made in modelling, and shed light on the complex problem of ligand-protein binding in the aqueous realm. 

Abstract In this paper, we report the first experimental observation of internal resonance in a dusty plasma, which shows the intrinsic nonlinearities of dust interactions in plasmas. When driving a system of vertically aligned dust particle pairs in the vertical direction, the horizontal motion is found to be excited during onset of internal resonance when the higher-frequency horizontal sloshing mode is nonlinearly coupled to the vertical breathing mode through the 1:2 commensurable relation. A theoretical model of the nonlinear interaction of dust particles in plasma is also provided and the results of the theoretical model are shown to match experimental observations.