Snapshot of the equilibrium dynamics of a drug bound to HIV-1 reverse transcriptase

The anti-AIDS drug rilpivirine undergoes conformational changes to bind HIV-1 reverse transcriptase and retain potency against drug-resistance mutations. Our discovery that water molecules play an essential role in the drug binding is reported. Femtosecond experiments and theory expose molecular level dynamics of rilpivirine bound to HIV-1 reverse transcriptase. The two nitrile substituents (-CN), one on each arm of the drug, have vibrational spectra consistent with their protein environments being similar in crystals and in solutions. Two-dimensional vibrational-echo spectroscopy reveals a dry environment for one nitrile while unexpectedly the other is hydrogen-bonded to a mobile water molecule, not identified in earlier X-ray structures. Ultrafast nitrile-water dynamics are confirmed by simulations. A higher (1.51 Å) resolution X-ray structure indeed reveals a water-drug interaction network. Maintenance of a crucial anchoring hydrogen bond, despite the enlargement and structural variation of the binding pocket, may help retain the potency of rilpivirine against the pocket mutations

The Connection Between Art, Healing, and Public Health: A Review of Current Literature

This review explores the relationship between engagement with the creative arts and health outcomes, specifically the health effects of music engagement, visual arts therapy, movement-based creative expression, and expressive writing. Although there is evidence that art-based interventions are effective in reducing adverse physiological and psychological outcomes, the extent to which these interventions enhance health status is largely unknown. Our hope is to establish a foundation for continued investigation into this subject and to generate further interest in researching the complexities of engagement with the arts and health