Review
Biophysics
Amnon Horovitz, Tali Haviv Reingewertz, Jorge Cuellar, Jose Maria Valpuesta
Summary: Chaperonins are essential nanomachines that assist in protein folding in an ATP-driven manner. Despite being intensively studied for more than three decades, the key aspects of their reaction mechanisms remain under debate. It is unclear whether there is a universal reaction mechanism for all substrates and whether it is passive or active.
ANNUAL REVIEW OF BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Yuchen Bai, Leina Dou, Weilin Wu, Zhimin Lu, Jiaqian Kou, Jianzhong Shen, Kai Wen, Zhanhui Wang
Summary: A novel strategy for sandwich immunoassay of beta-lactams with low molecular weights was proposed in this study. By selecting beta-lactam antibiotics to bind with penicillin binding protein (PBP)2x* and producing specific antibodies, the detection of 18 PBP2x*-beta-lactam complexes was successfully achieved with high sensitivity and wide working range. This study sheds light on further investigations for small-molecule detection using sandwich immunoassay.
Article
Environmental Sciences
Chi Zhang, Jinqiu Wu, Qinchang Chen, Haoyue Tan, Fuyan Huang, Jing Guo, Xiaowei Zhang, Hongxia Yu, Wei Shi
Summary: This study systematically summarizes the allosteric interactions between different EDCs and NRs, focusing on drugs belonging to the PPCP class, and discusses the advantages and hurdles of this new mechanism. Additionally, two strategies for virtual screening of numerous EDCs are highlighted, aiming to drive high-throughput and accurate screening of potential EDCs with non-competitive effects.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Oncology
Lijun Yao, Julia T. Wang, Reyka G. Jayasinghe, Julie O'Neal, Chia-Feng Tsai, Michael P. Rettig, Yizhe Song, Ruiyang Liu, Yanyan Zhao, Omar M. Ibrahim, Mark A. Fiala, Julie M. Fortier, Siqi Chen, Leah Gehrs, Fernanda Martins Rodrigues, Michael C. Wendl, Daniel Kohnen, Andrew Shinkle, Song Cao, Steven M. Foltz, Daniel Cui Zhou, Erik Storrs, Matthew A. Wyczalkowski, Smrithi Mani, Scott R. Goldsmith, Ying Zhu, Mark Hamilton, Tao Liu, Feng Chen, Ravi Vij, Li Ding, John F. DiPersio
Summary: This study utilizes single-cell transcriptomic profiling to identify potential therapeutic targets for multiple myeloma. The analysis identified 38 marker genes encoding cell-surface and intracellular proteins, including 11 previously uncharacterized targets. The findings provide valuable insights for the development of targeted antitumor therapy.
Article
Cell Biology
Jose Faro, Mario Castro
Summary: Current quantitative knowledge of antibody-mediated immunity is based on idealized experiments, but new experimental techniques often produce contradictory results, particularly in the field of T-cell receptors. The development of a mathematical framework has helped to rationalize these discrepancies and apply them to study the interactions between B-cell receptors and follicular dendritic cells during the germinal center reaction.
Article
Biochemistry & Molecular Biology
Erich Hellemann, Amrita Nallathambi, Jacob D. Durrant
Summary: Beta-lactam antibiotics target DD-transpeptidases, enzymes that perform the last step of bacterial cell-wall synthesis. To counteract these antibiotics, bacteria have evolved lactamases, such as TEM-1, that render them ineffective. In this study, molecular dynamics simulations were performed to investigate the inhibition of TEM-1 by an allosteric inhibitor, FTA. The simulations revealed a different conformation of FTA, compared to crystallographic observations, providing new insights into TEM-1 allosteric regulation.
Article
Immunology
Ganggang Bai, Yanhong Ge, Yuhong Su, Shuo Chen, Xingcheng Zeng, Huixia Lu, Buyong Ma
Summary: The study showed that the designed single-chain bispecific antibody can prevent the binding of SEB to TCR and thereby inhibit the formation of SEB-TCR and MHC II complexes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biophysics
Chunling Mao, Lei Wu, Yi Wen, Ximing Tang, Zheng Huang, Longshan Zhao
Summary: A photoelectrochemical immunosensor based on MIL-101(Cr) and CdTe-QDs composites was synthesized to detect the carcinoembryonic antigen (CEA) in human serum and urine samples. The sensor demonstrated altered photocurrent polarity, improved light utilization efficiency, and enhanced separation efficiency of electron-hole pairs. Under optimized conditions, the sensor showed high sensitivity and stability, with detection limits of 0.00018 ng mL-1 and 0.00023 ng mL-1 for anodic and cathodic detection of CEA, respectively.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Hematology
Andreas Greinacher, Kathleen Selleng, Raghavendra Palankar, Jan Wesche, Stefan Handtke, Martina Wolff, Konstanze Aurich, Michael Lalk, Karen Methling, Uwe Voelker, Christian Hentschker, Stephan Michalik, Leif Steil, Alexander Reder, Linda Schoenborn, Martin Beer, Kati Franzke, Andreas Buettner, Boris Fehse, Evi X. Stavrou, Chandini Rangaswamy, Reiner K. Mailer, Hanna Englert, Maike Frye, Thomas Thiele, Stefan Kochanek, Lea Krutzke, Florian Siegerist, Nicole Endlich, Theodore E. Warkentin, Thomas Renne
Summary: The mechanism underlying vaccine-induced immune thrombotic thrombocytopenia (VITT) primarily involves the formation of PF4/vaccine complexes and the proinflammatory environment stimulated by the vaccine, leading to the production of high-titer anti-PF4 antibodies in the body and consequent thrombosis.
Article
Chemistry, Organic
Shen-Yi Guo, Shuo Tong, Qing-Hui Guo, Mei-Xiang Wang
Summary: Despite the significant development of anion-pi interactions, the noncovalent interactions between fluoride ion and electron-neutral aromatic rings remain rare and controversial. This study presents the construction of electron-deficient corona[n]arenes and their selective fluoride recognition. The formation of a tetrazine radical anion and the influence of fluoride on water deprotonation in fluoride recognition are also reported.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Review
Endocrinology & Metabolism
Brice Beinsteiner, Isabelle M. L. Billas, Dino Moras
Summary: Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor that plays a crucial role in regulating liver-specific gene expression. Dysregulation of HNF4 is associated with human diseases like type I diabetes and hemophilia. This review focuses on the structures of HNF4 and its impact on the receptor's structure-function relationship.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Parasitology
Jennifer N. Lane, Annette Litster, Susan E. Little, Jessica Y. Rodriguez, Kennedy K. Mwacalimba, Kellee D. Sundstrom, E. Susan Amirian, Simone D. Guerios, Maria A. Serrano, Kellie M. Hays, Julie K. Levy
Summary: This study compared different methods for diagnosing HW infection in high-risk dogs, finding that combining POC Ag and Mf detection improved diagnostic performance, but may have missed more than one in four infected dogs.
PARASITES & VECTORS
(2021)
Article
Biochemistry & Molecular Biology
Shihao Yao, Qiuzi Yi, Boyuan Ma, Xiaoting Mao, Ye Chen, Min-Xin Guan, Xiaohui Cang
Summary: Through molecular dynamics simulations and sequence analysis, this study reveals a highly specific ADP binding site in the ADP/ATP carrier (AAC), explaining its unusually high substrate specificity and specific substrate selectivity for ADP. This finding provides new insights into the transport mechanism of AAC and other adenine nucleotide transporters, opening up new directions for further research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Mingfei Ji, Zongtao Chai, Jie Chen, Gang Li, Qiang Li, Miao Li, Yelei Ding, Shaoyong Lu, Guanqun Ju, Jianquan Hou
Summary: This study elucidated the effects of the SENP1 Q597A mutation on conformation, catalytic activity, and binding affinity of the SENP1-SUMO1 complex using molecular dynamics simulations and binding free energy calculations.
Article
Biochemistry & Molecular Biology
Ming-Tai Hu, Wen-Cong Ma, Jing-Han Wang, Xiao-Qing Jiang, Da-Qing Yang, Jian-Yang Ao
Summary: ZAP-70 is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transmit downstream signals. This study investigates the molecular mechanisms of allosteric inactivation of ZAP-70 induced by the W165C mutation, which reveals changes in protein dynamics and binding affinity. The findings provide insights into the pathological mechanism of ZAP-70.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Stefano A. Serapian, Alice Triveri, Filippo Marchetti, Matteo Castelli, Giorgio Colombo
Summary: Advances in genomics and proteomics have discovered numerous key proteins and mechanisms underlying pathologies. Changes in protein expression levels, mutations, and post-translational modifications can disrupt protein-protein interaction networks, influencing disease phenotypes. The challenges posed by undruggable targets require new molecular intervention approaches, such as perturbing pathogenic protein expression levels instead of blocking their activities.
Article
Biochemistry & Molecular Biology
Valentina Pirota, Chiara Platella, Domenica Musumeci, Alessandra Benassi, Jussara Amato, Bruno Pagano, Giorgio Colombo, Mauro Freccero, Filippo Doria, Daniela Montesarchio
Summary: NDI-5 has shown promising potential as a ligand for multimeric G4 structures, selectively targeting them over duplex DNA. Experimental analyses including CD, gel electrophoresis, ITC, and fluorescence spectroscopy suggest that NDI-5 effectively binds and stabilizes tel46 G4, favoring a hybrid folding in K+-containing buffer.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Physical
Mariarosaria Ferraro, Elisabetta Moroni, Emiliano Ippoliti, Silvia Rinaldi, Carlos Sanchez-Martin, Andrea Rasola, Luca F. Pavarino, Giorgio Colombo
Summary: The study utilized machine learning to uncover the relationship between different levels of allosteric inhibition and local dynamic patterns in the protein TRAP1, providing a new approach to infer the functionality of allosteric ligands. The combination of molecular dynamics and machine learning offers a promising strategy to support in silico mechanistic studies and drug design.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Physical
Filippo Marchetti, Elisabetta Moroni, Alessandro Pandini, Giorgio Colombo
Summary: Allosteric drugs have gained increasing interest, with high-throughput screening being a common practice for their discovery. Despite growing biological information and computational power, challenges remain in selecting allosteric ligands and predicting their impact on target protein function. Computational approaches typically involve molecular docking and molecular dynamics to recover information on the long-range regulation typical of allosteric proteins.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Review
Pharmacology & Pharmacy
Stefano A. Serapian, Carlos Sanchez-Martin, Elisabetta Moroni, Andrea Rasola, Giorgio Colombo
Summary: TRAP1, the mitochondrial isoform of heat shock protein (Hsp)90 chaperones, plays a crucial role in regulating metabolism and organelle homeostasis in various pathological states. Developing TRAP1-directed strategies, including lead modification with mitochondria delivery groups and computational discovery of allosteric sites and ligands, opens up unique opportunities in addressing fundamental questions on its biology and unveiling new therapeutic approaches. Predicting the activities of TRAP1-selective allosteric ligands and optimizing target engagement to avoid side effects are crucial in this endeavor.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Francesco Manoli, Filippo Doria, Giorgio Colombo, Barbara Zambelli, Mauro Freccero, Ilse Manet
Summary: The study investigated naphthalene diimide monomers and dyads as ligands of human telomeric DNA G4 structures and revealed their binding features at the G4 interface. In the absence of NMR and crystallographic data, the research provides important evidence of binding at the interface pocket and clues on the role played by the ligand structure.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Alice Triveri, Stefano A. Serapian, Filippo Marchetti, Filippo Doria, Silvia Pavoni, Fabrizio Cinquini, Elisabetta Moroni, Andrea Rasola, Francesco Frigerio, Giorgio Colombo
Summary: The SARS-CoV-2 spike protein is the prime target for Covid-19 vaccines due to its exposure on the viral surface. Variants of this protein have emerged, reducing the recognition by targeting antibodies and potentially impacting immunological treatments. By using molecular dynamics and structure-dynamics-energy strategies, researchers predicted changes in immunogenic regions on different S-protein variants, providing insights into the development of vaccines and antibodies to control emerging variants.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Multidisciplinary
Angela Bitonti, Rita Puglisi, Massimiliano Meli, Stephen R. Martin, Giorgio Colombo, Piero Andrea Temussi, Annalisa Pastore
Summary: Cold denaturation is a fundamental phenomenon in proteins, but it is only observed at temperatures above the freezing point of water in few cases. This study induced cold denaturation in a stable protein by introducing mutations and demonstrated the importance of electrostatic frustration in the mechanism of cold denaturation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Giulia Morra, Asghar M. Razavi, Anant K. Menon, George Khelashvili
Summary: Cholesterol inhibits the ability of GPCRs to scramble lipids by occupying a specific interface and stabilizing its conformation.
Article
Chemistry, Physical
Matteo Castelli, Filippo Doria, Mauro Freccero, Giorgio Colombo, Elisabetta Moron
Summary: Molecular dynamics simulations are valuable in studying nucleic acid structures. We analyze the factors that can limit the accuracy of MD simulations in studying G-quadruplex structures and conclude that the choice of force fields, ion parameters, ionic strengths, and water models all play important roles. We find that simulations with K+-ions to neutralize the system charge, mimicking intracellular ionic strength, and using the four-atom water model are the most accurate in reproducing experimental NMR constraints and data.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Luca Torielli, Stefano A. Serapian, Lara Mussolin, Elisabetta Moroni, Giorgio Colombo
Summary: Protein-protein interactions (PPIs) are important pharmacological targets for developing new therapeutics. This study presents a design strategy that combines the analysis of protein dynamics and energetics with docking and fragment combination to identify substructures involved in PPIs and generate PPI inhibitor candidates. The approach is validated using diverse PPI targets, and the hit molecules share high chemical similarity with experimentally tested inhibitors. This protocol provides a valuable means of generating initial leads against difficult targets for further development and refinement.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Om Shanker Tiwari, Ruth Aizen, Massimiliano Meli, Giorgio Colombo, Linda J. W. Shimon, Noam Tal, Ehud Gazit
Summary: Molecular self- and co-assembly have the ability to form diverse and well-defined supramolecular structures with notable physical properties. By exploring the co-assembly of L-His with different aromatic amino acids, including Phe, Tyr, and Trp, we expanded the structural space of amino acid nanomaterials. The best seamless co-assembly was observed between L-His and L-Phe, resulting in the formation of single crystals.
Article
Biochemistry & Molecular Biology
Federico Manai, Lisa Zanoletti, Giulia Morra, Samman Mansoor, Francesca Carriero, Elena Bozzola, Stella Muscianisi, Sergio Comincini
Summary: Celiac disease is an autoimmune disorder that affects the small intestine. It is caused by the ingestion of gluten, a storage protein found in wheat, barley, rye, and related cereals. Gluten exorphins (GEs), a group of biologically active peptides, have been proposed to contribute to asymptomatic CD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Physical
Federica Guarra, Giorgio Colombo
Summary: The design of new biomolecules that utilize immune mechanisms for disease treatment is a major challenge for computational and simulative approaches. Antibodies have emerged as an important class of therapeutics, particularly in cancer treatment and other diseases. This article provides a summary of the state-of-the-art computational approaches for designing antibodies and antigens, as well as key methodologies for identifying epitopes for B-cell and T-cell responses. The focus is on structure- and physics-based models, which are favored over purely sequence-based approaches. The implications of novel methods in engineering biomolecules with tailor-made immunological properties for therapeutic purposes are discussed. In addition, the integration of structure- and physics-based methods with emerging Artificial Intelligence technologies for predicting and designing novel antigens, epitopes, and antibodies presents extraordinary challenges and opportunities.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Barbara Gonzalez Teran, Maureen Pittman, Reuben Thomas, Franco Felix, Desmond Richmond-Buccola, Krishna Choudhary, Elisabetta Moroni, Colombo Giorgio, Arun Padmanabhan, Mauro Costa, Yu Huang, Michael Alexanian, Clara Lee, Bonie Cole, Kaitlen Samse-Knapp, Michael McGregor, Casey Gifford, Ruth Huttenhain, Bruce Gelb, Bruce Conklin