Predicting allosteric sites using fast conformational sampling as guided by coarse-grained normal modes [PDF]
, 2023 Wenjun Zheng
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Multi‐View Biomedical Foundation Models for Molecule‐Target and Property Prediction
Advanced Science, EarlyView.Molecular foundation models can provide accurate predictions for a large set of downstream tasks. We develop MMELON, an approach that integrates pre‐trained graph, image, and text foundation models and validate our multi‐view model on over 120 tasks, including GPCR binding.
Parthasarathy Suryanarayanan +17 more
wiley +1 more source
Chemical, target, and bioactive properties of allosteric modulation.
PLoS Computational Biology, 2014 Allosteric modulators are ligands for proteins that exert their effects via a different binding site than the natural (orthosteric) ligand site and hence form a conceptually distinct class of ligands for a target of interest.
Gerard J P van Westen +2 more
doaj +1 more source
Novel Allosteric Sites on Ras for Lead Generation
PLoS ONE, 2011 Aberrant Ras activity is a hallmark of diverse cancers and developmental diseases. Unfortunately, conventional efforts to develop effective small molecule Ras inhibitors have met with limited success. We have developed a novel multi-level computational approach to discover potential inhibitors of previously uncharacterized allosteric sites.
Grant, Barry J +6 more
openaire +6 more sources
Generating Dynamic Structures Through Physics‐Based Sampling of Predicted Inter‐Residue Geometries
Advanced Science, EarlyView.While static structure prediction has been revolutionized, modeling protein dynamics remains elusive. trRosettaX2‐Dynamics is presented to address this challenge. This framework leverages a Transformer‐based network to predict inter‐residue geometric constraints, guiding conformation generation via physics‐based iterative sampling. The resulting method
Chenxiao Xiang +3 more
wiley +1 more source
Eigenvector Centrality Distribution for Characterization of Protein Allosteric Pathways
, 2018 Determining the principal energy pathways for allosteric communication in biomolecules, that occur as a result of thermal motion, remains challenging due to the intrinsic complexity of the systems involved.
Batista, Victor S. +8 more
core
Advanced Science, EarlyView.Cytokine‐engineered CAR‐T cells represent a promising immunotherapy against malignancies due to direct tumor killing and potent immunity response. However, significant toxicities, including CRS and ICANS, have restricted clinical applications. How to keep the risk‐benefit balance of the advanced therapy is of great importance for maximizing the benefit
Xinru Zhang +7 more
wiley +1 more source
Engineering Fluoroacetate Dehalogenase by Growth‐Based Selections on Non‐Natural Organofluorides
Angewandte Chemie, EarlyView.We present a high‐throughput selection system to engineer fluoroacetate dehalogenases (FAcDs). By challenging E. coli populations that produce diverse FAcD libraries to grow on non‐natural organofluorides as their sole carbon source, we isolated a panel of FAcD variants with improved activity and altered substrate specificity.
Suzanne C. Jansen +2 more
wiley +2 more sources
Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor. [PDF]
, 2018 The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects.
Livingston, Kathryn E +4 more
core
Active Site Design and Exploitation of Allosteric Sites in Proteases
, 2021 Maureen E. Hill
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