Generation of a Nonbilayer Lipid Nanoenvironment after Epitope Binding Potentiates Neutralizing HIV-1 MPER Antibody.

Establishment of interactions with the envelope lipids is a cardinal feature of broadly neutralizing antibodies (bnAbs) that recognize the Env membrane-proximal external region (MPER) of HIV. The lipid envelope constitutes a relevant component of the full "quinary" MPER epitope, and thus antibodies may be optimized through engineering their capacity to interact with lipids. However, the role of the chemically complex lipid nanoenvironment in the mechanism of MPER molecular recognition and viral neutralization remains poorly understood.

Building predictive Markov models of ion channel permeation from molecular dynamics simulations.

Molecular dynamics (MD) simulation of biological processes has always been a challenging task due to the long timescales of the processes involved and the large amount of output data to handle. Markov state models (MSMs) have been introduced as a powerful tool in this area of research, as they provide a mechanistically comprehensible synthesis of the large amount of MD data and, at the same time, can be used to rapidly estimate experimental properties of biological processes. Herein, we propose a method for building MSMs of ion channel permeation from MD trajectories, which directly evaluates the current flowing through the channel from the model's transition matrix (T), which is crucial for comparing simulations and experimental data.

Insight from atomistic molecular dynamics simulations into the supramolecular assembly of the aldo-keto reductase from Trypanosoma cruzi.

Context: Currently, Chagas disease represents an important public health problem affecting more than 8 million people worldwide. The vector of this disease is the Trypanosoma cruzi (Tc) parasite. Our research specifically focuses on the structure and aggregation states of the enzyme aldo-keto reductase of Tc (TcAKR) reported in this parasite.

BRAZILIAN HERNIA AND ABDOMINAL WALL SOCIETY STATEMENT ON LARGE HIATAL HERNIAS MANAGEMENT.

Large hiatal hernias, besides being more prevalent in the elderly, have a different clinical presentation: less reflux, more mechanical symptoms, and a greater possibility of acute, life-threatening complications such as gastric volvulus, ischemia, and visceral mediastinal perforation. Thus, surgical indications are distinct from gastroesophageal reflux disease-related sliding hiatal hernias. Heartburn tends to be less intense, while symptoms of chest pain, cough, discomfort, and tiredness are reported more frequently.

Experimental and computational biophysics to identify vasodilator drugs targeted at TRPV2 using agonists based on the probenecid scaffold.

TRP channels are important pharmacological targets in physiopathology. TRPV2 plays distinct roles in cardiac and neuromuscular function, immunity, and metabolism, and is associated with pathologies like muscular dystrophy and cancer. However, TRPV2 pharmacology is unspecific and scarce at best.