Androgen receptor (AR) plays important roles in the development of prostate cancer (PCa). The antagonistic drugs, which suppress the activity of AR, are widely used in the treatment of PCa. However, the molecular mechanism of antagonism about how ligands affect the structures of AR remains elusive. To better understand the conformational variability of ARs bound with agonists or antagonists, we performed long time unbiased molecular dynamics (MD) simulations and enhanced sampling simulations for the ligand binding domain of AR (AR-LBD) in complex with various ligands. Based on the simulation results, we proposed an allosteric pathway linking ligands and helix 12 (H12) of AR-LBD, which involves the interactions among the ligands and the residues W741, H874, and I899. The interaction pathway provides an atomistic explanation of how ligands affect the structure of AR-LBD. A repositioning of H12 was observed, but it is facilitated by the C-terminal of H12, instead of by the loop between helix 11 (H11) and H12. The bias-exchange metadynamics simulations further demonstrated the above observations. More importantly, the free energy profiles constructed by the enhanced sampling simulations revealed the transition process between the antagonistic form and agonistic form of AR-LBD. Our results would be helpful for the design of more efficient antagonists of AR to combat PCa.

A charge-transfer-featured naphthalimide derivative with a small exchange energy but a lower lying (3)ππ* state than (3)CT state is found to contribute to triplet harvesting through a P-type rather than an E-type delayed fluorescence, and could act as a quite promising host to achieve highly efficient OLEDs.

The potential energy surface for the He–CO2 van der Waals complex is calculated using the fourth-order Moller–Plesset (MP4) perturbation theory with a large basis set containing bond functions. The interaction energies are obtained by the supermolecular approach with the full counterpoise correction for the basis set superposition error. The MP4 interaction energies are then fitted to an exponential-spline-Morse–Morse-spline-van der Waals potential form. The ab initio potential energy surface contains two local minima corresponding to the T-shaped and linear structures. The T-shaped minimum is the global minimum with the well depth of 44.41 cm−1 at R(He–C)=3.10 Å. The linear minimum has a well depth of 27.69 cm−1 at R(He–C)=4.26 Å. A potential barrier that separates the two minima is located at R(He–C)=4.10 Å and θ=39° with a height of 19.81 cm−1. The rovibrational energy levels of He–CO2 with CO2 at its ground state and υ3 excited state are calculated using the vibrational self-consistent field configuration-interaction approach. Our calculated results show that the potential supports five vibrational bound states. The zero-point energy is 28.60 cm−1. The first excited bend frequency is 8.67 cm−1, which is very close to the experimental estimated value of about 9±2 cm−1. The calculated transition frequencies and spectroscopic constants are in good agreement with the experimental values.

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