Key Laboratory Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
2 papers in the library · 11 citations · publishing 2025
The position of the hydroxyl group on the indole ring of psilocin analogs determines their ability to activate the 5-HT2A receptor and produce psychedelic-like effects. Analogs with the hydroxyl group at the 4th or 5th position (psilocin and bufotenine) show significantly higher agonistic activity and head-twitch responses than those with the group at the 6th or 7th position. Computer simulations reveal that the 4- and 5-position analogs form a crucial hydrogen bond with residue L229 and a stable salt bridge and hydrogen bond with residue D155, guiding them into the binding site. Analogs lacking these interactions fail to reach the orthosteric site and have poor receptor activity.
A new measure called Φcopula, which uses a Gaussian copula approach to estimate integrated information, outperforms common estimators by maintaining the lowest bias and mean squared error even in non-Gaussian high-dimensional systems. Applied to electroencephalographic data across awake, propofol-induced unresponsive, and NREM sleep states, alpha-band Φcopula significantly decreased during both anesthesia and sleep. Φcopula-based classifiers distinguished arousal states more accurately than functional connectivity and network efficiency measures. The dorsal attention network and default mode network contributed most to Φcopula, with the cingulate and posterior cortices showing the greatest contributions. The posterior cortex, especially the posterior cingulate cortex, appears critical for arousal-related information integration and consciousness.