Protein-polypeptide interactions, including those involving intrinsically-disordered peptides and intrinsically-disordered regions of protein binding partners, are crucial for many biological functions. However, experimental structure determination of protein-peptide complexes can be challenging. Computational methods, while promising, generally require experimental data for validation and refinement. Here we present CSP_Rank, an integrated modeling approach to determine the structures of...
[NMR paper] Time-optimized protein NMR assignment with an integrative deep learning approach using AlphaFold and chemical shift prediction
Time-optimized protein NMR assignment with an integrative deep learning approach using AlphaFold and chemical shift prediction
Chemical shift assignment is vital for nuclear magnetic resonance (NMR)-based studies of protein structures, dynamics, and interactions, providing crucial atomic-level insight. However, obtaining chemical shift assignments is labor intensive and requires extensive measurement time. To address this limitation, we previously proposed ARTINA, a deep learning method for automatic assignment of two-dimensional (2D)-4D NMR spectra. Here, we present an integrative...
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11-23-2023 10:09 AM
[NMR paper] Structure Determination of Challenging Protein-Peptide Complexes Combining NMR Chemical Shift Data and Molecular Dynamics Simulations
Structure Determination of Challenging Protein-Peptide Complexes Combining NMR Chemical Shift Data and Molecular Dynamics Simulations
Intrinsically disordered regions of proteins often mediate important protein-protein interactions. However, the folding-upon-binding nature of many polypeptide-protein interactions limits the ability of modeling tools to predict the three-dimensional structures of such complexes. To address this problem, we have taken a tandem approach combining NMR chemical shift data and molecular simulations to determine the structures of peptide-protein complexes. Here,...
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03-31-2023 09:21 AM
The measurement of binding affinities by NMR chemical shift perturbation
The measurement of binding affinities by NMR chemical shift perturbation
Abstract
We have carried out chemical shift perturbation titrations on three contrasting proteins. The resulting chemical shifts have been analysed to determine the best way to fit the data, and it is concluded that a simultaneous fitting of all raw shift data to a single dissociation constant is both the most accurate and the most precise method. It is shown that the optimal weighting of 15N chemical shifts to 1H chemical shifts is protein dependent, but is around the consensus...
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08-04-2022 01:03 AM
[NMR paper] The measurement of binding affinities by NMR chemical shift perturbation
The measurement of binding affinities by NMR chemical shift perturbation
We have carried out chemical shift perturbation titrations on three contrasting proteins. The resulting chemical shifts have been analysed to determine the best way to fit the data, and it is concluded that a simultaneous fitting of all raw shift data to a single dissociation constant is both the most accurate and the most precise method. It is shown that the optimal weighting of ^(15)N chemical shifts to ¹H chemical shifts is protein dependent, but is around the consensus value of 0.14. We show...
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08-04-2022 01:03 AM
[NMR paper] Structural model of the human BTG2-PABPC1 complex by combining mutagenesis, NMR chemical shift perturbation data and molecular docking
Structural model of the human BTG2-PABPC1 complex by combining mutagenesis, NMR chemical shift perturbation data and molecular docking
Degradation of cytoplasmic mRNA in eukaryotes involves the shortening and removal of the mRNA poly(A) tail by poly(A)-selective ribonuclease (deadenylase) enzymes. In human cells, BTG2 can stimulate deadenylation of poly(A) bound by cytoplasmic poly(A)-binding protein PABPC1. This involves the concurrent binding by BTG2 of PABPC1 and the Caf1/CNOT7 nuclease subunit of the Ccr4-Not deadenylase complex. To understand in molecular detail how PABPC1 and BTG2...
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06-01-2022 11:03 AM
[NMR paper] An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling
An Integrative Approach to Determine 3D Protein Structures Using Sparse Paramagnetic NMR Data and Physical Modeling
Paramagnetic nuclear magnetic resonance (NMR) methods have emerged as powerful tools for structure determination of large, sparsely protonated proteins. However traditional applications face several challenges, including a need for large datasets to offset the sparsity of restraints, the difficulty in accounting for the conformational heterogeneity of the spin-label, and noisy experimental data. Here we propose an integrative approach to structure determination combining...
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09-04-2021 10:34 AM
Using Chemical Shift Perturbation to Characterise Ligand Binding
Using Chemical Shift Perturbation to Characterise Ligand Binding
Available online 21 March 2013
Publication year: 2013
Source:Progress in Nuclear Magnetic Resonance Spectroscopy</br>
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Chemical shift perturbation (CSP, chemical shift mapping or complexation-induced changes in chemical shift, CIS) follows changes in the chemical shifts of a protein when a ligand is added, and uses these to determine the location of the binding site, the affinity of the ligand, and/or possibly the structure of the complex. A key factor in determining the appearance of spectra during...
Integrative Modeling of Protein-Polypeptide Complexes by Bayesian Model Selection using AlphaFold and NMR Chemical Shift Perturbation Data
Linear Mode
