Mechanical stress and anionic lipids synergistically stabilize an atypical structure of the angiotensin II type 1 receptor (AT1).

Environmental factors, including mechanical stress and surrounding lipids, can influence the response of GPCRs, such as the mechanosensitive angiotensin II type 1 receptor (AT1). To investigate the impact of these factors on AT1 activation, we developed a steered molecular dynamics simulations protocol based on quaternion formalism. In this protocol, a pulling force was applied to the N-terminus of transmembrane helix 6 (TM6) to induce the TM6 opening characteristic of activation.

[Bimodal model of delusional psychoses (on the problem of the correlation of paranoid dimensions in the psychopathological space of schizophrenia)].

Objective: To establish clinico-pathogenetic ratios of delusional psychoses constituting the psychopathological space of paranoid schizophrenia and to determine clinical and pathogenetic validity of concepts of a single delusional psychosis (a model of chronic delusion with a staged course) and two endogenous delusional psychoses.

Material And Methods: A sample consisted of 56 patients (19 women, 37 men; the average age 39.7±9.

Homology Modeling in the Twilight Zone: Improved Accuracy by Sequence Space Analysis.

The analysis of the relationship between sequence and structure similarities during the evolution of a protein family has revealed a limit of sequence divergence for which structural conservation can be confidently assumed and homology modeling is reliable. Below this limit, the twilight zone corresponds to sequence divergence for which homology modeling becomes increasingly difficult and requires specific methods. Either with conventional threading methods or with recent deep learning methods, such as AlphaFold, the challenge relies on the identification of a template that shares not only a common ancestor (homology) but also a conserved structure with the query.

Identification of Dysregulated Expression of G Protein Coupled Receptors in Endocrine Tumors by Bioinformatics Analysis: Potential Drug Targets?

Background: Many studies link G protein-coupled receptors (GPCRs) to cancer. Some endocrine tumors are unresponsive to standard treatment and/or require long-term and poorly tolerated treatment. This study explored, by bioinformatics analysis, the tumoral profiling of the GPCR transcriptome to identify potential targets in these tumors aiming at drug repurposing.