Article
Engineering, Biomedical
Bibin Anand, Qi Wu, Maryam Nakhaei-Nejad, Govindarajan Karthivashan, Lyudmyla Dorosh, Sara Amidian, Abhishek Dahal, Xiuju Li, Maria Stepanova, Holger Wille, Fabrizio Giuliani, Satyabrata Kar
Summary: Native PLGA nanoparticles show therapeutic potential in the treatment of Alzheimer's disease by suppressing aggregation of beta-amyloid peptides, triggering their disassembly, reducing phosphorylation of tau protein, enhancing neuronal viability, and attenuating memory deficits and A beta levels in animal models of AD.
BIOACTIVE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Siddhartha Banerjee, Mohtadin Hashemi, Karen Zagorski, Yuri L. Lyubchenko
Summary: The presence of cholesterol in lipid bilayers significantly enhances the aggregation process of Aβ42 at low concentrations, indicating that the lipid composition plays a crucial role in controlling the self-assembly of Aβ oligomers in cellular membranes.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Mohtadin Hashemi, Siddhartha Banerjee, Yuri L. Lyubchenko
Summary: The effects of membranes on the early-stage aggregation of amyloid beta (A beta) have been studied, showing that direct A beta-membrane interactions dramatically enhance the aggregation process. Cholesterol in membranes significantly enhances the aggregation kinetics and accelerates the formation and dissociation of aggregates. Cholesterol binds A beta monomers and changes their conformation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jean-Numa Gillet
Summary: The study unravels the binding mechanisms of APOE4 associated with Alzheimer's disease, showing that when bound to the amyloid-beta peptide, APOE4 undergoes misfolding and increased deposition, potentially leading to the disease. Immunotherapies targeting APOE4 are promising for drug design, but the focus should be on non-lipidated APOE4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Medicinal
Angelo Santoro, Manuela Grimaldi, Michela Buonocore, Ilaria Stillitano, Anna Maria D'Ursi
Summary: This study utilized NMR to analyze the conformational transition of A beta(1-42) in 50/50 HFIP/water, revealing unexpected routes in the evolution from helical to beta-sheet structures. Molecular dynamics simulations confirmed that the structural model calculated in this study is a starting point for amyloid fibrils formation.
Article
Biochemistry & Molecular Biology
Xingyuan Zou, Sebastian Himbert, Alix Dujardin, Janos Juhasz, Samantha Ros, Harald D. H. Stover, Maikel C. Rheinstadter
Summary: The study found that curcumin and homotaurine can effectively reduce the aggregation of amyloid beta and have no observable impact on brain membranes. These drugs inhibit A beta aggregation by changing membrane properties and binding to A beta peptides. Membrane-lipid therapy may be an effective approach to inhibit peptide aggregation.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Dimitris Matiadis, See-Ting Ng, Eric H-L Chen, Georgia Nigianni, Veroniki P. Vidali, Aleksander Canko, Rita P-Y Chen, Marina Sagnou
Summary: Ten hydroxylated monocarbonyl curcumin derivatives were designed, synthesized, and evaluated for their NEP upregulating potential, with compound 4 showing the highest activity. Derivatives bearing a cyclohexanone group exhibited higher activity enhancement compared to their acetone counterparts.
Review
Biochemistry & Molecular Biology
Anna Sulatskaya, Anastasiia O. Kosolapova, Alexander G. Bobylev, Mikhail Belousov, Kirill S. Antonets, Maksim Sulatsky, Irina M. Kuznetsova, Konstantin K. Turoverov, Olesya Stepanenko, Anton A. Nizhnikov
Summary: Both amyloids and beta-barrel proteins have beta-sheet-rich structures, with the latter being able to form functional amyloids in vivo. These beta-barrel amyloid proteins can interact with each other and form toxic oligomers, potentially contributing to the development of amyloidoses. Rapidly growing discoveries suggest that the number and diversity of functions of amyloid-forming beta-barrel proteins are significantly greater than currently understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lei Gu, Zhefeng Guo
Summary: Formation of amyloid oligomers and fibrils, underlying neurodegenerative diseases like Alzheimer's, involves interactions with cellular membranes. The conversion of Aβ42 globulomers to fibrils in the presence of DOPC liposomes suggests a dynamic nature of interactions between Aβ oligomers and membranes. Lipid membranes can reduce membrane-disrupting activities caused by Aβ oligomers by converting them to fibrils.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Environmental Sciences
Samal Kaumbekova, Mehdi Amouei Torkmahalleh, Dhawal Shah
Summary: It is hypothesized that airborne particulate matter and ultrafine particles can influence the early onset and progression of Alzheimer's disease by impacting the aggregation of amyloid beta peptides. Molecular dynamics simulations revealed that ultrafine particles affected the aggregation of Aβ(16-21) peptides differently based on the type of ions present in the simulation environment. The presence of certain ions such as SO4-2 and NO3- accelerated the aggregation of Aβ(16-21) peptides in the presence of C-60, while NH4+ ions decelerated their aggregation.
ENVIRONMENTAL POLLUTION
(2021)
Article
Biochemistry & Molecular Biology
Vahid Zarezade, Zahra Nazeri, Shirin Azizidoost, Maryam Cheraghzadeh, Hossein Babaahmadi-Rezaei, Alireza Kheirollah
Summary: In this study, the effects of A beta on ABCA1 protein levels were investigated in microglia, astrocytes, and neurons using in vitro and in silico experiments. It was found that A beta significantly increased the protein levels of ABCA1 in these cells, but decreased its ability to efflux cholesterol. Molecular docking and molecular dynamics simulation revealed that A beta inhibited the function of ABCA1 by obstructing the extracellular tunnel.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Nan Yuan, Lianmeng Ye, Yan Sun, Hao Wu, Zhengpan Xiao, Wanmeng Fu, Zuqian Chen, Yechun Pei, Yi Min, Dayong Wang
Summary: The major pathological feature of Alzheimer's disease (AD) is the aggregation of amyloid beta peptide (A beta) in the brain. Inhibition of A beta(42) aggregation may prevent the advancement of AD. This study found that arginine dipeptide (RR) was the most effective at interfering with A beta(42) polymerization and reducing its toxicity, including cell death, reactive oxygen species (ROS) production, and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Willy Smeralda, Marc Since, Julien Cardin, Sophie Corvaisier, Sophie Lecomte, Christophe Cullin, Aurelie Malzert-Freon
Summary: The study focused on the molecular interactions between the amyloid beta peptide associated with Alzheimer's disease and biological membranes, developing simple liposomal formulations mimicking neuronal cell membranes. Characterization of interactions through a multiparametric procedure laid the methodological foundation for developing an original model describing interactions between A beta peptide and lipids.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Satoru Itoh, Hisashi Okumura
Summary: Aggregates of amyloid-beta (Aβ) peptides are enhanced at hydrophilic-hydrophobic interfaces and inhibited by polyphenols. Aβ40 accelerates aggregation due to its beta-hairpin structure, while polyphenols inhibit Aβ(16-22) aggregation by forming hydrogen bonds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Satoru G. Itoh, Maho Yagi-Utsumi, Koichi Kato, Hisashi Okumura
Summary: It has been found that two additional C-terminal residues in Aβ42 play a significant role in its faster aggregation compared to Aβ40. Through molecular dynamics simulations, a key residue, Arg5, was identified for the dimerization process of Aβ42. Amino acid substitutions of Arg5 were found to remarkably suppress the aggregation of both Aβ42 and Aβ40. Therefore, the two additional C-terminal residues alter the role of Arg5 in the oligomerization process.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Alexa M. Salsbury, Justin A. Lemkul
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Chemistry, Multidisciplinary
Remy Pawlak, J. G. Vilhena, Philipp D'Astolfo, Xunshan Liu, Giacomo Prampolini, Tobias Meier, Thilo Glatzel, Justin A. Lemkul, Robert Haner, Silvio Decurtins, Alexis Baratoff, Ruben Perez, Shi-Xia Liu, Ernst Meyer
Article
Biochemistry & Molecular Biology
Justin A. Lemkul
NUCLEIC ACIDS RESEARCH
(2020)
Article
Chemistry, Physical
Alexa M. Salsbury, Tanner J. Dean, Justin A. Lemkul
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Chemistry, Medicinal
Brian D. Ratnasinghe, Alexa M. Salsbury, Justin A. Lemkul
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Chemistry, Medicinal
Molly Congdon, Russell G. Fritzemeier, Yugesh Kharel, Anne M. Brown, Vlad Serbulea, David R. Bevan, Kevin R. Lynch, Webster L. Santos
Summary: Elevated levels of Sphingosine 1-phosphate (S1P) and increased expression of Sphingosine kinase iso-forms (SphK1 and SphK2) are associated with various disease states. The development of selective inhibitors for SphK1 and SphK2 has become a focus of drug discovery, with studies focusing on optimizing binding in the SphK2 substrate binding site. The identification of indole-based compounds with 1,5-disubstitution as potent inhibitors highlights the potential for targeting SphK2 with improved potency and selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biophysics
Alexa M. Salsbury, Justin A. Lemkul
Summary: Nucleic acid-ion interactions play a crucial role in the structure and function of DNA and RNA. Molecular dynamics simulations reveal that potassium ions bind more effectively than sodium and lithium ions in G-quadruplexes, with a faster binding rate.
BIOPHYSICAL JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Abhishek A. Kognole, Jumin Lee, Sang-Jun Park, Sunhwan Jo, Payal Chatterjee, Justin A. Lemkul, Jing Huang, Alexander D. MacKerell, Wonpil Im
Summary: The Drude Prepper tool has been developed in CHARMM-GUI to facilitate the use of polarizable FF based on the classic Drude oscillator model. It allows for easy construction of Drude FF-based PSF and generation of input for MD simulations using various simulation packages. The stability and effectiveness of the Drude Prepper protocol and inputs have been demonstrated through validation with a variety of heterogeneous systems.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Marcelo D. Poleto, Justin A. Lemkul
Summary: We introduce TUPA, a Python-based algorithm for calculating and analyzing electric fields in molecular simulations. We also provide a PyMOL plugin to visualize electric fields within the simulation system. The features of TUPA are demonstrated through three test cases where the electric field exerted by biomolecules helps explain biological phenomena or observed kinetics.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Marcelo D. Poleto, Justin A. Lemkul
Summary: This paper reviews the successes and difficulties in the development of additive and polarizable force fields, discusses the availability of experimental data, and highlights possible routes to further improve the accuracy of force fields.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Physical
Alexsandra N. Corrigan, Justin A. Lemkul
Summary: Intrinsically disordered proteins (IDPs) are abundant and play crucial regulatory roles in biological processes. This study used the Drude-2019 force field to simulate the interactions between the p53 transactivation domain and two protein partners, revealing the importance of electrostatic interactions in IDP protein-protein interactions.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Alexa M. Salsbury, Haley M. Michel, Justin A. Lemkul
Summary: This study used polarizable simulations to investigate telomeric DNA structures, including G-quadruplexes and G-hairpins. The presence of specific motifs, such as the G-triad, in the telomeric G-quadruplex suggests potential druggable sites. In addition, the simulations showed the unbiased formation of G-triad and G-tetrad in the G-hairpin, and the involvement of cations in their formation. Furthermore, the study demonstrated the specific interactions between K+ ions and guanine bases, providing new insights into the influence of ions on telomeric DNA structures.
Article
Chemistry, Medicinal
Marcelo D. Poleto, Justin A. Lemkul
Summary: G-quadruplexes (GQs) are noncanonical nucleic acid structures formed by guanine-rich sequences in DNA and RNA. They play crucial roles in gene regulation and maintenance. This study used various simulation techniques to investigate the impact of ion binding on GQ dynamics and revealed subtle differences between DNA and RNA GQs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Andras F. Wacha, Justin A. Lemkul
Summary: CHARMM is widely used in biomolecular forcefields and can be used with other codes. This article presents an automated and validated method for converting the CHARMM force field to a format readable by the GROMACS engine, harmonizing the capabilities of the two codes with minimal user interaction.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Microbiology
Ariana Umana, Justin A. Lemkul, Daniel J. Slade
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2019)