Advances in bioconjugation and native protein modification are appearing at a blistering pace, making it increasingly time consuming for practitioners to identify the best chemical method for modifying a specific amino acid residue in a complex setting. The purpose of this perspective is to provide an informative, graphically rich manual highlighting significant advances in the field over the past decade. This guide will help triage candidate methods for peptide alteration and will serve as a starting point for those seeking to solve long-standing challenges.
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http://dx.doi.org/10.1021/acs.biochem.7b00536 | DOI Listing |
bioRxiv
December 2024
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Machine learning has emerged as a promising approach for predicting molecular properties of proteins, as it addresses limitations of experimental and traditional computational methods. Here, we introduce GSnet, a graph neural network (GNN) trained to predict physicochemical and geometric properties including solvation free energies, diffusion constants, and hydrodynamic radii, based on three-dimensional protein structures. By leveraging transfer learning, pre-trained GSnet embeddings were adapted to predict solvent-accessible surface area (SASA) and residue-specific p values, achieving high accuracy and generalizability.
View Article and Find Full Text PDFAnal Chem
December 2024
Department of Chemistry, Sogang University, Seoul 04107, Republic of Korea.
Radical-directed protein fragmentation techniques, particularly free radical-initiated peptide sequencing (FRIPS) mass spectrometry (MS), offer significant potential for elucidating protein structures in the gas phase. This study presents a novel approach to protein structural analysis in vacuo, combining FRIPS MS with genetic code expansion (GCE) technology. By incorporating unnatural amino acids (UAAs) at specific sites within an Affibody protein, we effectively introduced a radical precursor at six distinct positions.
View Article and Find Full Text PDFACS Phys Chem Au
November 2024
Department of Physics, Bryn Mawr College, Bryn Mawr, Pennsylvania 19010, United States.
Protein dynamics in the unfolded state, in the context of early stage protein folding or intrinsically disordered proteins (IDPs), is not well understood. The discovery of IDPs, and their sequence-dependent dynamics, has led to many computational and experimental investigations regarding the conformational preferences of short oligopeptides and individual amino acid residues in the unfolded state. As proteins consist of sequences of amino acid residues, characterizing the intrinsic conformational preferences of the individual residues in the unfolded state is crucial for understanding the emergent conformations of peptides and proteins.
View Article and Find Full Text PDFCytokine
January 2025
JSPS Government Homeopathic Medical College, Hyderabad 500013, India. Electronic address:
CD40-CD40-ligand (CD40L) interaction plays crucial immunoregulatory roles, as CD40 signals through different signaling intermediates to convert the messages from CD40L to effector functions. Being a TNFα receptor family member, CD40 binds TNFα receptor-associated factors, assembles signalosome complexes and decrypts the messages from CD40L through different signaling modules to result in residue-specific effector functions. The evidence for such a residue-specific message encryption first came from the CD40L mutations resulting in X-linked hyper-IgM syndrome, as the extent of effects varied with the residue mutated.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
November 2024
Department of Chemistry and the Institute of Macromolecular Assembly, York College of the City University of New York, Jamaica, New York 11451, United States; PhD Programs in Chemistry, Graduate Center of the City University of New York, NY, New York, 10016, United States; PhD Programs in Biochemistry, Graduate Center of the City University of New York, NY, New York, 10016, United States. Electronic address:
Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA.
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