A General Picture of Cucurbit[8]uril Host-Guest Binding: Recalibrating Bonded Interactions.

Atomic-level understanding of the dynamic feature of host-guest interactions remains a central challenge in supramolecular chemistry. The remarkable guest binding behavior of the Cucurbiturils family of supramolecular containers makes them promising drug carriers. Among Cucurbit[]urils, Cucurbit[8]uril (CB8) has an intermediate portal size and cavity volume.

Seeding the multi-dimensional nonequilibrium pulling for Hamiltonian variation: indirect nonequilibrium free energy simulations at QM levels.

The combination of free energy simulations in the alchemical and configurational spaces provides a feasible route to access the thermodynamic profiles under a computationally demanding target Hamiltonian. Normally, due to the significant differences between the computational cost of quantum mechanics (QM) calculations and those of semi-empirical quantum mechanics (SQM) and molecular mechanics (MM), this indirect method could be used to obtain the QM thermodynamics by combining the SQM or MM results and the SQM-to-QM or MM-to-QM corrections. In our previous work, a multi-dimensional nonequilibrium pulling framework for Hamiltonian variations was introduced based on bidirectional pulling and bidirectional reweighting.

A General Picture of Cucurbit[8]uril Host-Guest Binding.

Describing, understanding, and designing complex interaction networks within macromolecular systems remain challenging in modern chemical research. Host-guest systems, despite their relative simplicity in both the structural feature and interaction patterns, still pose problems in theoretical modeling. The barrel-shaped supramolecular container cucurbit[8]uril (CB8) shows promising functionalities in various areas, e.

SAMPL6 host-guest binding affinities and binding poses from spherical-coordinates-biased simulations.

Host-guest binding is a challenging problem in computer simulation. The prediction of binding affinities between hosts and guests is an important part of the statistical assessment of the modeling of proteins and ligands (SAMPL) challenges. In this work, the volume-based variant of well-tempered metadynamics is employed to calculate the binding affinities of the host-guest systems in the SAMPL6 challenge.

Sulfur-substitution-induced base flipping in the DNA duplex.

Base flipping is widely observed in a number of important biological processes. The genetic codes deposited inside the DNA duplex become accessible to external agents upon base flipping. The sulfur substitution of guanine leads to thioguanine, which alters the thermodynamic stability of the GC base pairs and the GT mismatches.

BAR-based multi-dimensional nonequilibrium pulling for indirect construction of a QM/MM free energy landscape.

Construction of free energy landscapes at the quantum mechanics (QM) level is computationally demanding. As shown in previous studies, by employing an indirect scheme (i.e.