AIMC Topic: Allosteric Regulation

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Machine Learning of Allosteric Effects: The Analysis of Ligand-Induced Dynamics to Predict Functional Effects in TRAP1.

The journal of physical chemistry. B
Allosteric molecules provide a powerful means to modulate protein function. However, the effect of such ligands on distal orthosteric sites cannot be easily described by classical docking methods. Here, we applied machine learning (ML) approaches to ...

Coupling dynamics and evolutionary information with structure to identify protein regulatory and functional binding sites.

Proteins
Binding sites in proteins can be either specifically functional binding sites (active sites) that bind specific substrates with high affinity or regulatory binding sites (allosteric sites), that modulate the activity of functional binding sites throu...

Prediction of Orthosteric and Allosteric Regulations on Cannabinoid Receptors Using Supervised Machine Learning Classifiers.

Molecular pharmaceutics
Designing highly selective compounds to protein subtypes and developing allosteric modulators targeting them are critical considerations to both drug discovery and mechanism studies for cannabinoid receptors. It is challenging but in demand to have c...

Perturbation Theory/Machine Learning Model of ChEMBL Data for Dopamine Targets: Docking, Synthesis, and Assay of New l-Prolyl-l-leucyl-glycinamide Peptidomimetics.

ACS chemical neuroscience
Predicting drug-protein interactions (DPIs) for target proteins involved in dopamine pathways is a very important goal in medicinal chemistry. We can tackle this problem using Molecular Docking or Machine Learning (ML) models for one specific protein...

Probing light chain mutation effects on thrombin via molecular dynamics simulations and machine learning.

Journal of biomolecular structure & dynamics
Thrombin is a key component for chemotherapeutic and antithrombotic therapy development. As the physiologic and pathologic roles of the light chain still remain vague, here, we continue previous efforts to understand the impacts of the disease-associ...

Harnessing Allostery to Modulate Protein-Protein Interactions: From Function to Therapeutic Innovations.

Journal of molecular biology
Protein-protein interactions (PPIs) are ubiquitous mediators of cellular functions, and their dysregulation is central to numerous pathological conditions. Traditional drug discovery strategies targeting PPIs directly have faced considerable obstacle...

Synthetic Biology for Designing Allostery and Its Potential Biomedical Applications.

Journal of molecular biology
Allosteric regulation of protein function, where a perturbation at one site induces a conformational shift or alters dynamics at a distal functional site, plays a key role in numerous biological processes. The ability to introduce allostery using syn...

Artificial Intelligence Captures Pseudo-Intelligence Evolved in the Chemical Architecture of the Multifaceted Signal Transducer, TAK1.

Journal of chemical information and modeling
TAK1, a multifunctional kinase, possesses intramolecular interactions that are capacitated to recognize and process diverse forms of chemical and mechanical forces, which ultimately translate into a convergent catalytic function. By elucidating a dua...

Deep Learning-Guided Discovery of Celestolide as a Natural Allosteric Inhibitor Targeting CYP51 and Its Application in Strawberry Preservation.

Journal of agricultural and food chemistry
Most CYP51 inhibitors act competitively and are prone to resistance, whereas allosteric inhibitors hold promise but are difficult to develop. In this study, we employed the neural relational inference framework alongside the Gaussian network-based de...

Computer-Aided Drug Discovery for Undruggable Targets.

Chemical reviews
Undruggable targets are those of therapeutical significance but challenging for conventional drug design approaches. Such targets often exhibit unique features, including highly dynamic structures, a lack of well-defined ligand-binding pockets, the p...