Article
Biochemistry & Molecular Biology
Miriam Weckener, Laura S. Woodward, Bradley R. Clarke, Huanting Liu, Philip N. Ward, Audrey Le Bas, David Bhella, Chris Whitfield, James H. Naismith
Summary: The study reveals the regulatory mechanism of polysaccharide polymerization in Enterobacteriaceae bacteria. It demonstrates the formation of a complex between WzyE polymerase and WzzE polysaccharide co-polymerase, which together participate in the polymerization and regulation of polysaccharides. These findings provide important structural insights into the mechanism of polysaccharide chain length regulation in bacteria.
Article
Biochemistry & Molecular Biology
Andrew Santiago-Frangos, Murat Buyukyoruk, Tanner Wiegand, Pushya Krishna, Blake Wiedenheft
Summary: The study found multiple IHF binding sites and diverse upstream sequence motifs in CRISPR leaders, crucial for CRISPR adaptation. The phase of motifs was shown to be critical for CRISPR adaptation.
Article
Microbiology
Sirui Han, Kailun Guo, Wei Wang, Yizhi J. Tao, Haichun Gao
Summary: In this study, HtpA was identified as a heme-trafficking protein in the bacterium Shewanella oneidensis. The absence of HtpA significantly reduced cytochrome c content and catalase activity. This research sheds light on the mechanism of heme transport across membranes in bacteria and extends the understanding of TANGO2 proteins.
Review
Biochemical Research Methods
Rananjaya S. Gamage, Jordan L. Chasteen, Bradley D. Smith
Summary: This article summarizes the different ways that proteins are anchored in cell membranes and the strategies used to label membrane proteins in living cells. It also describes the methods used to produce lipidated proteins. A three-component synthetic construct composed of a lipophilic membrane anchor, hydrophilic linker, and exposed functional component is used to anchor the payload on the cell surface. Hydrocarbon chains are commonly used as the membrane anchor and amphiphilic fluorescent dyes with a zwitterionic linker have high persistence in living cell membranes. A new advance is the development of switchable membrane anchors for fundamental studies and applied biomaterials.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Takuma Kanamaru, Kazuo Sakurai, Shota Fujii
Summary: In cancer chemotherapy, core-cross-linked particles (CCPs) show promise as drug carriers due to their high structural stability in vivo. Coating the surface of CCPs with a biocompatible polymer, polyethylene glycol (PEG), avoids nonspecific protein adsorption. Our study found that the PEG density and conformation did not significantly affect the in vivo pharmacokinetics and pharmacodynamics of PEGylated CCPs. However, the release kinetics of hydrophilic and hydrophobic model drugs from the PEGylated CCPs were strongly influenced by the PEG conformation and drug polarity.
Review
Biochemistry & Molecular Biology
Andreas Haahr Larsen
Summary: Eukaryotic cells contain membranes with various curvatures, which are generated and sustained by specific proteins, peptides, and lipids. In addition, certain molecules can sense membrane curvature. Molecular dynamics simulations provide a valuable tool for investigating curved lipid membranes and their interactions with membrane-associated proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Long Li, Jinglei Hu, Xinghua Shi, Bartosz Rozycki, Fan Song
Summary: The binding of receptors and ligands in biological cells has been found to reduce the energy threshold for lipid clusters to coalesce into mesoscale domains, leading to significant cooperativity in receptor-ligand binding. This interplay between binding cooperativity and lipid domain formation results in acute sensitivity of the membrane system to changes in control parameters, which could be crucial in cell signaling and immune responses.
Article
Food Science & Technology
Chontida Tangsongcharoen, Jose L. Toca-Herrera, Boonhiang Promdonkoy, Sudarat Tharad
Summary: This study investigated the importance of the conserved T144 residue in the alpha D-beta 4 loop of Cyt2Aa2 protein for lipid binding on fluid lipid membranes. The results showed that replacing threonine with alanine hinders the binding of Cyt2Aa2 on liquid lipid membranes, providing a possibility to modify the protein to specific cells via lipid phase selection.
Article
Multidisciplinary Sciences
Kyle I. P. Le Huray, He Wang, Frank Sobott, Antreas C. Kalli
Summary: This study systematically simulated the interactions between 100 mammalian PH domains and PIP-containing membranes. The observed PIP interaction hotspots recapitulate crystallographic binding sites and provide insights into the mechanisms of PH domain/membrane association. The study offers a comprehensive view of the binding of PH domains to membranes.
Article
Biochemistry & Molecular Biology
Xavier Prasanna, Veijo T. Salo, Shiqian Li, Katharina Ven, Helena Vihinen, Eija Jokitalo, Ilpo Vattulainen, Elina Ikonen
Summary: Seipin can trap TAGs in the ER bilayer via its luminal hydrophobic helices, serving as a catalyst for seeding the TAG cluster and generating a favorable promethin binding interface.
Article
Chemistry, Physical
Minoru Nakano, Hiroyuki Nakao, Shigeharu Yoshida, Masakazu Fukuda, Manjiro Imai, Keisuke Ikeda
Summary: This study investigates the dynamic changes of lipids with membrane curvature, revealing that lipids in membranes with high positive curvature have unique packing properties, resulting in enhanced hydrophobic hydration and increased activation entropy. These findings provide important insights into the functions and structural changes of biomembranes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Juan Nicolas-Espinosa, Lucia Yepes-Molina, Fuensanta Martinez-Bernal, Miriam Fernandez-Pozurama, Micaela Carvajal
Summary: This study aimed to investigate the physiological response of broccoli leaves to abiotic stresses such as salinity and boron toxicity/deficiency. The results showed that the combined stress of salinity and boron deficiency resulted in a significant reduction in plant biomass, and the adaptation mechanisms were associated with water and boron concentration in the leaves. The expression patterns of PIP aquaporins varied among the different stress treatments, and their presence in the plasma membrane and interaction with the lipid environment played potential regulatory roles in facilitating salinity-boron stress adaptation mechanisms.
Article
Immunology
Nicholas T. Funderburg, Carey L. Shive, Zhengyi Chen, Curtis Tatsuoka, Emily R. Bowman, Chris T. Longenecker, Grace A. McComsey, Brian M. Clagett, Dominic Dorazio, Michael L. Freeman, Scott F. Sieg, Daniela Moisi, Donald D. Anthony, Jeffrey M. Jacobson, Sharon L. Stein, Leonard H. Calabrese, Alan Landay, Charles Flexner, Keith W. Crawford, Edmund Capparelli, Benigno Rodriguez, Michael M. Lederman
Summary: Inhibition of IL-6 activity by tocilizumab has significant effects on immune activation/inflammation and lipid profiles in people with treated HIV infection.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Katarzyna Makasewicz, Stefan Wennmalm, Bjorn Stenqvist, Marco Fornasier, Alexandra Andersson, Peter Jonsson, Sara Linse, Emma Sparr
Summary: Cooperative binding is a crucial feature in metabolic pathways, signaling, and transport processes, allowing for tight regulation over a narrow concentration range. The study shows strong positive cooperativity of alpha-synuclein binding to phospholipid membranes, indicating that the protein has a higher affinity for a membrane where there is already bound protein, compared to a bare membrane.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Cell Biology
Jenifer Monks, David J. Orlicky, Andrew E. Libby, Monica Dzieciatkowska, Mark S. Ladinsky, James L. McManaman
Summary: This study uncovers the molecular mechanisms of LD-APM interactions and highlights the role of Perilipin-2 in apocrine lipid secretion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Chemistry, Analytical
Pieter De Gauquier, Kenno Vanommeslaeghe, Yvan Vander Heyden, Debby Mangelings
Summary: This article presents an overview of molecular modelling approaches for chiral separations on polysaccharide-based and macrocyclic antibiotic chiral selectors. Both atomistic calculations and empirical fitting procedures are discussed. Atomistic calculations, such as docking and molecular dynamics, can provide insights into the chiral recognition mechanism by modeling the interactions between enantiomers and the chiral stationary phase. On the other hand, empirical fitting procedures involve mathematical models that are fitted to experimental observations using theoretical molecular descriptors. These models can be used to predict a specific response, such as retention, in chiral separations. The article also discusses different regression models, such as multiple linear regression and partial least squares.
ANALYTICA CHIMICA ACTA
(2022)
Article
Chemistry, Physical
Yeol Kyo Choi, Nathan R. Kern, Seonghan Kim, Krishan Kanhaiya, Yaser Afshar, Sun Hee Jeon, Sunhwan Jo, Bernard R. Brooks, Jumin Lee, Ellad B. Tadmor, Hendrik Heinz, Wonpil Im
Summary: Molecular modeling and simulation are important tools for predicting properties and understanding mechanisms of nanomaterials. However, building nanomaterial-containing systems is challenging. Researchers have developed a web-based nanomaterial modeler that generates transferable nanomaterial models among different simulation packages. The modeler has been validated and can also generate complex systems of nanomaterial-biomolecule and nanomaterial-polymer interfaces.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Physical
Cheol Jeong, Ryan Franklin, Karen J. Edler, Kenno Vanommeslaeghe, Susan Krueger, Joseph E. Curtis
Summary: Lipid nanodiscs are promising reagents to solubilize membrane proteins in nativelike environments and characterize them. Small-angle neutron scattering can determine the low-resolution structures of proteins, and contrast variation methods can enhance this process. It is possible to eliminate the scattering of the nanodisc by tuning the neutron scattering length densities.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Medicinal
Irina D. Pogozheva, Grant A. Armstrong, Lingyang Kong, Timothy J. Hartnagel, Carly A. Carpino, Stephen E. Gee, Danielle M. Picarello, Amanda S. Rubin, Jumin Lee, Soohyung Park, Andrei L. Lomize, Wonpil Im
Summary: We conducted a comparative study using molecular dynamics simulations to investigate the effects of sterols and lipid unsaturation on the structural and mechanical properties of biomembranes. The study provides valuable insights into water permeation and the correlation between membrane properties and composition. The findings are important for understanding the behavior and function of biomembranes.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Payal Chatterjee, Mert Y. Sengul, Anmol Kumar, Alexander D. MacKerell
Summary: The outcomes of computational chemistry and biology research are greatly influenced by the choice of forcefield used in molecular simulations. This study develops a deep learning-based framework for optimizing van der Waals interactions in molecular simulations. The resulting LJ parameters (interactions between atoms) are validated for their performance in reproducing condensed phase thermodynamic properties and demonstrate improved accuracy in reproducing solvent and crystal properties.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Asuka A. Orr, Suliman Sharif, Junmei Wang, Alexander D. MacKerell
Summary: Generalized force fields (FFs) are extensions of biomolecular FFs used for organic molecules. However, their application to arbitrary molecules requires caution to ensure their integrity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Abhishek A. Kognole, Anthony Hazel, Alexander D. MacKerell
Summary: RNA molecules can be potential drug targets in various diseases due to their dysregulated expression or misfolding. Noncoding RNAs, which account for a large part of the human genome, have complex structures and can be targeted by small molecules. The SILCS computational approach, termed SILCS-RNA, was extended to target RNA in this study and evaluated against seven RNA targets. The method provides detailed functional group affinity patterns and facilitates the identification of new potential binding sites and ligand design.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Physical
Wenbo Yu, David J. Weber, Alexander D. MacKerell
Summary: Covalent drug design plays a significant role in drug discovery by forming a covalent bond with targeted residues, leading to a more effective therapeutic approach. Computational methods can identify reactive residues, test potential reactivities, and predict noncovalent contributions to binding. SILCS, a functional group mapping approach, considers protein flexibility, functional group, and protein desolvation along with functional group-protein interactions. SILCS-Covalent, an integrated workflow, can qualitatively and quantitatively inform covalent drug discovery.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Yalun Yu, Richard M. Venable, Jonathan Thirman, Payal Chatterjee, Anmol Kumar, Richard W. Pastor, Benoit Roux, Alexander D. MacKerell Jr, Jeffery B. Klauda
Summary: Accurate empirical force fields of lipid molecules are crucial for molecular dynamics simulations of various lipid systems and heterogeneous systems. The polarizable Drude force field has been optimized in this study to improve its accuracy in simulating pure bilayers and membranes. By using both experimental and quantum mechanical data, the optimized force field shows good agreement with a range of experimental observables. The polarizable Drude2023 force field is anticipated to advance our understanding of electronic polarization in lipid systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Shasha Feng, Soohyung Park, Yeol Kyo Choi, Wonpil Im
Summary: Molecular dynamics simulations are important for understanding drug binding and action mechanisms in membranes and membrane proteins. CHARMMGUI Membrane Builder has the potential to generate complex membrane assemblies and meet the demands of current research.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Mingtian Zhao, Abhishek A. Kognole, Sunhwan Jo, Aoxiang Tao, Anthony Hazel, Alexander D. MacKerell Jr
Summary: In this study, the sampling efficiency of the GCMC method was improved by applying known cavity-bias and configurational-bias algorithms on GPU architecture. The method was parallelized using CUDA and OpenCL, resulting in simultaneous sampling of a large number of configurations during insertion attempts. The partitioning scheme allowed for simultaneous insertion attempts for large systems, significantly improving efficiency. The algorithm was shown to be useful in the application of the site-identification by ligand competitive saturation (SILCS) co-solvent sampling approach for the protein CDK2.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Asuka A. Orr, Aoxiang Tao, Olgun Guvench, Alexander D. MacKerell
Summary: Protein-based therapeutics often face challenges of protein aggregation and high solution viscosity due to high concentrations of active protein. The charge of a protein, affected by its environment, plays a significant role in these solution behaviors. This study presents a structure-based approach called SILCS-Biologics, which predicts the effective charge of proteins by considering the competition between ions and the presence of buffers.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Mert Y. Sengul, Alexander D. MacKerell
Summary: Metal ions, particularly Mg2+, play a role in stabilizing RNA's tertiary structures. However, the atomic-level mechanisms underlying this process are not fully understood. In this study, computational techniques were combined to investigate the specific interactions between Mg2+ ions and RNA, particularly in the pseudoknot structure of the Twister ribozyme.
Article
Chemistry, Physical
Soohyung Park, Ilya Levental, Richard W. Pastor, Wonpil Im
Summary: The affinity of TM proteins for ordered membrane phases is influenced by lipidation, TM length, and lipid accessible surface area. In this study, the raft affinities of a TM domain and its depalmitoylated variant were assessed using free energy simulations. The results showed that both peptides preferentially partition into the liquid disordered phase and the detailed substructure of the liquid ordered phase modulates peptide partitioning.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Soohyung Park, Amy Rice, Wonpil Im, Richard W. Pastor
Summary: Peptides and proteins play crucial roles in membrane remodeling by inducing spontaneous curvature. This study successfully estimates the peptide-induced spontaneous curvature using specific boundary conditions.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)