AIMC Topic: Allosteric Site

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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 ...

Integrated structural modeling and super-resolution imaging resolve GPCR oligomers.

Progress in molecular biology and translational science
Formation of G protein-coupled receptors (GPCRs) dimers and higher order oligomers represents a key mechanism in pleiotropic signaling, yet how individual protomers function within oligomers remains poorly understood. For the Class A/rhodopsin subfam...

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...

Recognition of protein allosteric states and residues: Machine learning approaches.

Journal of computational chemistry
Allostery is a process by which proteins transmit the effect of perturbation at one site to a distal functional site upon certain perturbation. As an intrinsically global effect of protein dynamics, it is difficult to associate protein allostery with...

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...

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...

DeepAllo: allosteric site prediction using protein language model (pLM) with multitask learning.

Bioinformatics (Oxford, England)
MOTIVATION: Allostery, the process by which binding at one site perturbs a distant site, is being rendered as a key focus in the field of drug development with its substantial impact on protein function. The identification of allosteric pockets (site...

ASD2023: towards the integrating landscapes of allosteric knowledgebase.

Nucleic acids research
Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible onli...

DeepAlloDriver: a deep learning-based strategy to predict cancer driver mutations.

Nucleic acids research
Driver mutations can contribute to the initial processes of cancer, and their identification is crucial for understanding tumorigenesis as well as for molecular drug discovery and development. Allostery regulates protein function away from the functi...