Molecular dynamics simulations reveal the coupling of quinone dynamics to protein conformational changes in respiratory complex I

Recently, a kind of synthetic chloride-transporting mono-squaramide (CTMS) was found to induce apoptosis as well as disrupt autophagy. In order to improve the solubility of this potential anticancer agent, developing a suitable method is of great significance. In this work, quantum mechanics (QM) calculations and molecular dynamics (MD) simulations were used to explore the inclusion process of CTMS into cucurbit[n]uril (CB[n], n = 6, 7, and 8) in the gaseous phase and aqueous solution. According to the results from theoretical calculation, the encapsulation process of CTMS into all three CB[n] hosts is thermodynamically feasible. The Solvent effect was considered in water using the PCM method. It is found that these encapsulated systems have good solubility and stability. Furtherly, the cavity of CB[7] turns out to be a perfect match with CTMS in both phases. The electrophilicity based charge transfer (ECT) analysis indicates that CTMS can be adsorbed into CB[n] with a charge transfer from CB[n] to CTMS. The obtained MD results illustrate that the host and guest could spontaneously adsorption during the dynamic simulation. The independent gradient model (IGM) result confirms that the van der Waals interactions and hydrogen bonds play a major role in the stabilizing of the physisorption complexes. The results show that CB[7] could be a promising candidate for the delivery of CTMS. The present work might provide a suitable carrier to improve the solubility of CTMS.