Article
Biochemistry & Molecular Biology
Yeng-Tseng Wang, Tian-Lu Cheng
Summary: MDM2 and MDMX are potential targets for p53-dependent cancer therapy. Researchers used advanced computational methods to investigate the interactions between MDM2/MDMX and cyclic peptide-based inhibitors, aiming to improve the accuracy of peptide-protein structural prediction for cyclic peptide drug design. Advancements in computing power and methods hold promise for addressing challenges in cyclic peptide drug design.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Physical
Arthur Voronin, Alexander Schug
Summary: Despite significant progress in experimental techniques, protein structure determination remains a challenging task. Computer simulations are often used to complement or interpret experimental data, with many methods providing highly accurate protein structure models. Research focuses on selecting representative members or ensembles from computationally generated structures.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Harutyun Sahakyan, Karen Nazaryan, Arcady Mushegian, Irina Sorokina
Summary: Molecular dynamics simulations were performed to study protein folding. By applying rotational force to the C-terminal amino acid while restricting the movement of the N-terminal amino acid, the folding of four protein domains was accelerated at least by an order of magnitude. These results suggest that external forces and constraints can bias the motions of the polypeptide and facilitate the attainment of stable fold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yen-Hua Huang, Qingdan Du, Zhihao Jiang, Gordon J. King, Brett M. Collins, Conan K. Wang, David J. Craik
Summary: A single point mutation of residue Ile-11 to Leu or Gly significantly increased the folding yields of bracelet cyclotides, allowing for the synthesis of mirror image enantiomers and the elucidation of their crystal structures using quasi-racemic crystallography. This study provides a facile strategy to produce bracelet cyclotides and access their atomic resolution structures easily, laying a foundation for the development of biotechnological applications.
Article
Biochemistry & Molecular Biology
Hamed Abdollahi, James H. Prestegard, Homayoun Valafar
Summary: Solution nuclear magnetic resonance spectroscopy is a powerful tool for studying biomolecules in water environments. Residual dipolar couplings (RDCs) allow for the analysis of motion characteristics, and their acquisition and computational analysis have gained significant momentum in recent years. RDCs have been used to confirm internal dynamics, characterize the type of dynamics, and recover structural ensembles for conformational sampling.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elvis Awuni
Summary: Protein-protein interactions have become promising targets for alternative drugs. Peptide-based PPI inhibitors have been developed as the next-generation therapeutics to combat antimicrobial resistance. This study used computer modeling strategies to predict key MreB-CbtA interactions to facilitate the design of antiMreB peptide candidates.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Paola Turina, Piero Fariselli, Emidio Capriotti
Summary: The study of protein folding is crucial for understanding protein function and the relationship between genetics and phenotypes. K-Pro is a new database that collects experimental kinetic data on monomeric proteins with a two-state folding mechanism. It provides a user-friendly interface for browsing and downloading relevant data.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lukas Rohland, Roman Kityk, Luka Smalinskaite, Matthias P. Mayer
Summary: The 70 kDa heat shock proteins (Hsp70s) are versatile molecular chaperones that assist in protein-folding processes. ATP and cochaperones induce structural rearrangements in Hsp70, with peptides causing larger changes and protein clients being more effective in stimulating ATP hydrolysis. The study provides insights into the mechanics, allostery, and dynamics of Hsp70 chaperones.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Irina Artsimovitch, Cesar A. Ramirez-Sarmiento
Summary: Metamorphic proteins present unexpected paradigms in protein folding, as their sequences encode two alternative folds that can reversibly interconvert and trigger different cellular responses. This phenomenon may be common among proteins that need to respond to rapidly changing environments. This article summarizes the structural and functional evidence of RfaH as a metamorphic protein, describes the molecular mechanism and refolding pathways of its structural interconversion, and discusses ongoing efforts to identify signatures and general properties of the protein metamorphome.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Agriculture, Multidisciplinary
Abraham Vidal-Limon, Jose E. Aguilar-Toala, Andrea M. Liceaga
Summary: The use of in silico tools, such as molecular docking, to study biological activity of proteins and peptides can sometimes produce results that do not correlate with actual experimental binding affinities. Molecular dynamics simulations (MDS) offer a solution to overcome sampling limitations in docking analysis and provide valuable information in deciphering functional mechanisms of proteins and peptides. This review discusses the traditional use of in silico models, like molecular docking, and highlights the importance of MDS in predicting structural and functional dynamics of food proteins and bioactive peptides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Dailu Chen, Sofia Bali, Ruhar Singh, Aleksandra Wosztyl, Vishruth Mullapudi, Jaime Vaquer-Alicea, Parvathy Jayan, Shamiram Melhem, Harro Seelaar, John C. van Swieten, Marc I. Diamond, Lukasz A. Joachimiak
Summary: This study reveals the structural mechanism underlying spontaneous aggregation of FTD-tau mutant S320F, using a combination of in vitro, in silico, and cellular experiments. The study shows that S320F stabilizes a local hydrophobic cluster, exposing the amyloid motif (306)VQIVYK(311); identifies a suppressor mutation that reverses the phenotype in vitro and in cells; and computationally optimizes nonpolar clusters surrounding the S320 position to engineer tau sequences that spontaneously aggregate. This research uncovers a mechanism for regulating tau aggregation and may contribute to the design of reagents targeting disease-specific tau conformations.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Anirban Das, Anju Yadav, Mona Gupta, R. Purushotham, Vishram L. Terse, Vicky Vishvakarma, Sameer Singh, Tathagata Nandi, Arkadeep Banerjee, Kalyaneswar Mandal, Shachi Gosavi, Ranabir Das, Sri Rama Koti Ainavarapu, Sudipta Maiti
Summary: By constructing a xenonucleus based on specific design principles, the refolding speed of ubiquitin protein can be increased. This method provides a new approach for constructing specific folding catalysts for proteins with well-defined folding nuclei.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Physical
Lim Heo, Collin F. Arbour, Giacomo Janson, Michael Feig
Summary: Protein structures can be determined experimentally or computationally. Computational methods utilize databases for structure prediction, but predicting structures distant from known ones may result in lower accuracy. Physics-based refinement methods can improve model accuracy.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Shawn C. C. Hsueh, Adekunle Aina, Andrei Yu. Roman, Neil R. Cashman, Xubiao Peng, Steven S. Plotkin
Summary: Effectively presenting epitopes on immunogens is crucial in treating protein misfolding diseases. Computational modeling of cyclic peptide scaffolds can predict their conformational ensembles, allowing for selective targeting of toxic conformations while sparing healthy forms of the protein. Screening and ranking these cyclic peptide scaffolds in silico can provide insights into their suitability as immunogens.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yan Xu, Runshan Kang, Luyao Ren, Lin Yang, Tongtao Yue
Summary: By analyzing the changes in knotted conformation during protein folding and unfolding, several barriers that jointly suppress knot untying are revealed. Protein unfolding always precedes knot untying and primarily starts from separation of two alpha-helices (alpha 1 and alpha 5). These results provide new molecular level insights into the folding/unfolding of knotted proteins.