SummaryTarget recognition in RNA silencing is governed by the “seed sequence” of a guide RNA strand associated with the PIWI/MID domain of an Argonaute protein in RISC. Using a reconstituted in vitro target recognition system, we show that a model PIWI/MID domain protein confers position-dependent tightening and loosening of guide-strand-target interactions. Over the seed sequence, the interaction affinity is enhanced up to ˜300-fold. Enhancement is achieved through a reduced entropy penalty for the interaction. In contrast, interactions 3′ of the seed are inhibited. We quantified mismatched target recognition inside and outside the seed, revealing amplified discrimination at the third position in the seed mediated by the PIWI/MID domain. Thus, association of the guide strand with the PIWI/MID domain generates an enhanced affinity anchor site over the seed that can promote fidelity in target recognition and stabilize and guide the assembly of the active silencing complex.

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Helical supramolecular architectures play important structural and functional roles in biological systems. Although their occurrence is widely perceived to correlate to fundamental chiral units including l-amino acids and d-sugars, the detailed relationship between molecular and supramolecular handedness is still unclear. At the same time, although achiral units are practically always in close proximity to chiral ones by covalent linkage along a polymeric chain, their effect on supramolecular handedness has received relatively less attention. Here, we designed a set of short amphiphilic peptides, in which an achiral glycine residue was incorporated at the interface between the hydrophobic and hydrophilic segments. We observed that glycine incorporation caused dramatic variations in suprastructural handedness in self-assembled peptide nanofibrils, and the effect of the hydrophilic charged residue at the C-terminus on supramolecular handedness was demolished, leading to chiral truncation. Furthermore, molecular dynamics simulations and quantum chemistry calculations revealed that the unanticipated role of the glycine residue in regulating supramolecular handedness originated from its effect on the conformational preference of single β-strands. Importantly, reduced density gradient analyses on single β-strands indicated that, due to the lack of a side chain in glycine, intricate noncovalent interactions were produced among the neighboring amino acid side chains of the incorporated glycine and its local backbone, resulting in diverse β-strand conformations.

Asphaltene precipitation is a common phenomenon in the exploitation of crude oil and closely correlates with oil recovery, especially in CO2 flooding. In this work, employing molecular dynamics simulations, the asphaltene precipitation process in CO2 was investigated. The simulation results reveal that the CO2 could stepwise extract nonpolar and light polar components from asphaltene micelle, and a two-step asphaltene precipitation process was illustrated. In our eight molecule asphaltene system, first four asphaltene dimers formed. Two dimers get together into one aggregation in bulk; the other two dimers get together and adsorbed onto the silica surface. After that, the surface aggregation further induces the adsorption of bulk aggregation onto it to complete asphaltene precipitation. In addition, we also studied the pressure effect on asphaltene precipitation. Our work provided a molecular-level understanding of asphaltene precipitation phenomenon in CO2 flooding, and the results have significant promise for oil exploitation.