In recent years, improvements in experimental techniques and enhancements in computing power have revolutionized our understanding of the mechanisms of protein folding. By combining insights gained from theory, experiment and simulation we are moving toward an atomistic view of folding landscapes. Future challenges involve exploiting the knowledge gained and methods developed to enable us to elucidate a molecular description of folding dynamics in the complex environment of the cell.
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http://dx.doi.org/10.1038/nsmb.1592 | DOI Listing |
Biochim Biophys Acta Mol Basis Dis
January 2025
Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Cole-Carpenter syndrome (CCS) is a rare autosomal-dominant genetic disease characterized by craniosynostosis, ocular proptosis, hydrocephalus, distinctive facial features, and bone fragility. Previous cases of CCS are associated with genetic variations in P4HB, which encodes the protein disulfide isomerase (PDI), a key enzyme in protein folding. Patients with CCS caused by P4HB mutations often present with short stature, limb deformities, and abnormal epiphyseal plates.
View Article and Find Full Text PDFJ Pharm Sci
January 2025
Laboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.. Electronic address:
Post translational modifications (PTMs) of proteins play an integral role in maintaining the overall structure and function of proteins including their proper folding, binding, and potency. However, not all PTMs play a positive role in protein drugs as some can lead to product-related impurities that negatively impact protein function. One example of a PTM is trisulfide formation, which appears as a product related species in multiple biologic drug products.
View Article and Find Full Text PDFJ Gen Virol
January 2025
Unidad de Medicina Molecular, Instituto de Biomedicina de UCLM (IB-UCLM), Universidad de Castilla-La Mancha (UCLM), Albacete, Spain.
Translation errors, impaired folding or environmental stressors (e.g. infection) can all lead to an increase in the presence of misfolded proteins.
View Article and Find Full Text PDFJ Biomol Struct Dyn
January 2025
School of Medicine, Sari Branch, Islamic Azad University, Sari, Iran.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the formation of Lewy bodies, which are primarily composed of misfolded α-Synuclein (α-Syn). DJ-1 is a crucial protein involved in the correct folding of α-Syn, and mutations impairing its function are associated with the onset of PD. One such mutation, the L166P substitution in DJ-1, which has been linked to early-onset PD and results in the loss of DJ-1's homodimer structure.
View Article and Find Full Text PDFJ Chem Theory Comput
January 2025
School of Chemistry, Tel Aviv University, Tel Aviv 6997801, Israel.
We present a procedure for enhanced sampling of molecular dynamics simulations through informed stochastic resetting. Many phenomena, such as protein folding and crystal nucleation, occur over time scales inaccessible in standard simulations. We recently showed that stochastic resetting can accelerate molecular simulations that exhibit broad transition time distributions.
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