Mining the Potential of Label-Free Biosensors for In Vitro Antipsychotic Drug Screening

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The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...

Reinforcement learning (RL) is crucial for learning to adapt to new environments. In RL, the prediction error is an important component that compares the expected and actual rewards. Dopamine plays a critical role in encoding these prediction errors. In my ...

Medical research and technological advancements are heading towards tailored healthcare approaches that prioritize individual needs, allowing for more accurate diagnoses, more effective treatments, and better patient outcomes overall. One such approach is ...

Retinoblastoma, while relatively rare, stands as the most prevalent intraocular cancer. In Switzerland, the survival rate approaches 100%, but it drops to less than 50% in low-income countries. The current treatment options for retinoblastoma rely on a lim ...

Synthetic biology aims to engineer cells as miniature biological devices to sense, process, and respond to exogenous stimuli. Protein switches are designed to sense and respond to various molecular queues in a fast and specific manner, which fits the requi ...

The determination of intracellular drug concentrations can provide a better understanding of the drug function and efficacy. Ideally, this should be performed nondestructively, with no modification of either the drug or the target, and with the capability ...

Objective: Depotentiation of homosynaptic plasticity of the primary motor cortex (M1) is impaired in patients with Parkinson's disease (PD) who have developed dyskinesias. In this exploratory study, we tested whether this holds true for heterosynaptic plas ...

Targeting cells specific to type and state remains a challenge in developing effective therapies, sensitive diagnostics, also robust and versatile tissue engineering. A promising strategy is to focuses on improving the inherent selectivity of the targeting ...

Dopamine signals are thought to be important for reward-based learning and appear to play important roles in regulating synaptic plasticity in the nucleus accumbens and the striatum. However, the precise neuronal circuit mechanisms underlying the learning ...

Numerous key biological processes rely on the concept of multivalency, where ligands achieve stable binding only upon engaging multiple receptors. These processes, like viral entry or immune synapse formation, occur on the diffusive cellular membrane. One ...

In the past 10 years, our laboratory has proved the shine-through paradigm to be a very sensitive endophenotype for schizophrenia. The shine-through paradigm is a visual backward masking task, where the target is a vertical vernier followed by a 25-element ...

Here, the authors use smFRET to assess the structural dynamics of metabotropic glutamate receptor mGlu2 and show that a positive allosteric modulator or the Gi protein stabilize mGlu2 in the glutamate-induced active state, leading to the full activation of ...

G protein-coupled receptors (GPCRs) are 7-transmembrane alpha-helical integral membrane proteins on which cells heavily rely to receive information regarding their external environment. These receptors are able to transfer information to intracellular down ...

Alpha-synuclein oligomerization is one of the early events on the pathway to Lewy body formation. Therefore, interfering with this process holds tremendous potential for developing therapies that block alpha-Syn pathology formation and toxicity. The develo ...

The therapeutic efficacy and pharmacokinetics of antibody-drug conjugates (ADCs) in general, and antibody-oligonucleotide conjugates (AOCs) in particular, depend on the drug-to-antibody ratio (DAR) distribution and average value. The DAR is considered a cr ...

For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...

Metal ions, such as Na+, Mg2+, Ca2+, and Zn2+, are highly abundant in biological systems. For many G protein-coupled receptors (GPCRs), metal ions, especially Na+, have been found to stabilize the receptors' inactivate state preventing receptor activation. ...

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease(1)and antipsychotic drugs(2). DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine(3), leading to stimulation of G(i) ...

G protein-coupled receptors play essential roles in cellular processes such as neuronal signaling, vision, olfaction, tasting, and metabolism. As GPCRs are the most important drug targets, understanding their interactions with ligands is of utmost importan ...

Mining the Potential of Label-Free Biosensors for In Vitro Antipsychotic Drug Screening

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From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

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