Article
Biochemistry & Molecular Biology
Catia A. Bonito, Ricardo J. Ferreira, Maria-Jose U. Ferreira, Jean-Pierre Gillet, M. Natalia D. S. Cordeiro, Daniel J. V. A. dos Santos
Summary: In this study, the impact of four P-gp mutations on drug-binding and efflux-related signal-transmission mechanism was evaluated. The repacking of the transmembrane helices induced by mutations and ligands indicates P-gp's sensitivity to perturbations in the transmembrane region. Changes in drug-binding were observed as a consequence of transmembrane helices repacking, but were not always correlated with alterations in ligand binding mode and affinity. The changes in drug efflux are mostly related to changes in drug specificity rather than effects on signal-transmission mechanism.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Medicine, Research & Experimental
Laust Moesgaard, Peter Reinholdt, Carsten Uhd Nielsen, Jacob Kongsted
Summary: Considerable effort has been devoted to the search for modulators of membrane transport proteins. This study focuses on the inhibitory effect of polysorbate 20 (PS20) on P-glycoprotein (P-gp) and aims to understand the underlying molecular mechanism. Molecular dynamics simulations revealed that the hydrophobic nature of PS20 drives its binding to the drug-binding domain of P-gp, resulting in the inhibition of the protein's function.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Shafi Mahmud, Md. Jahirul Islam, Md. Rimon Parves, Md. Arif Khan, Lamiya Tabussum, Sinthyia Ahmed, Md. Ackas Ali, Sayo O. Fakayode, Mohammad A. Halim
Summary: This study aimed to identify potent inhibitors of P-glycoprotein using computational approaches. Two compounds showed promising anti-tumor activity with acceptable pharmacokinetic properties, and molecular docking and dynamics simulations verified their stable binding with P-glycoprotein. Principal component analysis and QSAR modeling provided insights into the interactions and predictive capabilities of the drug candidates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Ramprasad Misra, Ishita Das, Andras Der, Gabor Steinbach, Jin-gon Shim, Wayne Busse, Kwang-Hwan Jung, Laszlo Zimanyi, Mordechai Sheves
Summary: The presence of highly conserved tryptophan residues in microbial rhodopsins is crucial for the charge distribution, quantum yield, photocycle, and absorption properties of the retinal chromophore. Mutations of these residues to non-aromatic leucine or phenylalanine result in increased sensitivity to photobleaching, lower trans-cis photoisomerization yield, and altered photocycle kinetics. These findings suggest that protein-retinal interactions mediated by these tryptophan residues play a key role in achieving efficient light-induced retinal isomerization.
Article
Biochemistry & Molecular Biology
Mahmoud A. A. Ibrahim, Khlood A. A. Abdeljawaad, Laila A. Jaragh-Alhadad, Hesham Farouk Oraby, Mohamed A. M. Atia, Othman R. Alzahrani, Gamal A. H. Mekhemer, Mahmoud F. Moustafa, Ahmed M. Shawky, Peter A. Sidhom, Alaa H. M. Abdelrahman
Summary: The development of multidrug resistance (MDR) caused by overexpression of P-glycoprotein (P-gp/ABCB1/MDR1) is the main reason for the failure of chemotherapy in carcinoma treatment. An in silico study was conducted to discover potential P-gp inhibitors by assessing the binding energies of 512 drug candidates. Five promising drug candidates, valspodar, dactinomycin, elbasvir, temsirolimus, and sirolimus, showed strong binding energies against P-gp transporter and displayed good pharmacokinetic properties. These results indicate their potential as prospective P-gp inhibitors and require further in vitro/in vivo investigations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Sergio M. Marques, Lucie Supolikova, Lenka Molcanova, Karel Smejkal, David Bednar, Iva Slaninova
Summary: In this study, a computational approach was used to construct the full-length three-dimensional structure of human P-gp and refine it with molecular dynamics. Through docking experiments, certain natural flavonoids were identified as effective P-gp inhibitors, increasing the accumulation of doxorubicin in cancer cells and enhancing its antiproliferative activity.
Article
Chemistry, Physical
Manmeet Singh, Himanshu Verma, Priyanka Bhandu, Manoj Kumar, Gera Narendra, Shalki Choudhary, Pankaj Kumar Singh, Om Silakari
Summary: During the ongoing pandemic, there is an increasing number of reports on invasive fungal disease among immunocompromised populations. This study focused on optimizing the anti-fungal activity of a benzothiazole derivative and identified potential targets using network analysis. In vitro evaluation showed that two compounds exhibited improved anti-fungal activity.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Shihao Pang, Jiawei Liu, Tianlong Li, Kai Ye, Zexin Yan, Li Zhao, Chunyan Bao
Summary: This study reports an artificial receptor that achieves controllable ON/OFF signal transduction through conformational changes, providing a new model for constructing artificial signal transduction systems.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Meng Yu, Wei Si, Tao Zeng, Chang Chen, Xiaojing Lin, Zhouxiang Ji, Fei Guo, Yuxiang Li, Jingjie Sha, Yuliang Dong
Summary: This research used all-atom molecular dynamic simulations to uncover the microscopic mechanism behind current variation when single-stranded DNA passes through the MspA nanopore. It was found that nucleotide orientation and the region below the constriction of the nanopore play crucial roles in inducing current variation. These findings provide valuable insights for developing low-cost, high-throughput nanopore DNA sequencing technology.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Ye-Guang Fang, Xiaojiao Li, Yurui Gao, Yan-Hong Cui, Joseph S. S. Francisco, Chongqin Zhu, Wei-Hai Fang
Summary: We present an efficient method based on an extension of metadynamics for exploring complex free energy landscapes. The method greatly improves the performance of the metadynamics approach and allows for efficient modeling of chemical systems with complex free energy landscapes.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Liadys Mora Lagares, Yunierkis Perez-Castillo, Nikola Minovski, Marjana Novic
Summary: P-gp is an important protein involved in drug efflux and multidrug resistance. Molecular dynamics simulations can provide valuable insights into the binding behavior and conformational changes of P-gp in the presence of different compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Changli Yi, Chengzhi Hu, Lin Shi, Minli Bai, Yubai Li, Dawei Tang
Summary: Due to its excellent anti-friction and anti-wear properties, nano-MoS2 is considered to have great potential in lubrication, such as being used as a nano-additive in lubricating oil or solid lubricants. Through molecular dynamics simulation, the lubrication mechanism of MoS2 was explained from an atomic perspective, showing how it reduces friction coefficient and wear. The proposed mechanism provides a reference for the further application of MoS2 in lubrication.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Shirin Mollazadeh, Farzin Hadizadeh, Ricardo J. Ferreira
Summary: The study found that the stereochemistry of 1,4-dihydropyridines (DHPs) affects their binding ability with P-glycoprotein (P-gp) and can also impact the permeation and accumulation of drugs in cell membranes. Therefore, the stereochemistry should not be overlooked during the development of novel 1,4-dihydropyridine derivatives.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Multidisciplinary Sciences
Mohammad Khedri, Mostafa Keshavarz Moraveji
Summary: This study investigated the self-assembly of polymeric nanoparticles for drug delivery systems and successfully loaded an antitumor drug onto a targeting ligand. The results revealed a correlation between polymer molecular weight and particle stability, and confirmed the improvement of drug delivery to receptors and cancerous cells by the targeting ligand.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Applied
Chengzhi Liu, Nan Lv, Gerui Ren, Ruibo Wu, Binju Wang, Zexing Cao, Hujun Xie
Summary: The study investigated the binding mechanism of zein with EGCG, revealing that static quenching is the main interaction mode. Molecular dynamics simulation showed that EGCG prefers to bind to a pocket of zein formed by specific residues, with electrostatic and van der Waals interactions playing a dominant role in the binding. This research provides new insights into the interaction mechanism between zein and EGCG, which is crucial for developing plant protein as a tea polyphenol delivery system.
FOOD HYDROCOLLOIDS
(2021)
Article
Biochemistry & Molecular Biology
Philipp Grad, Katarina Edwards, Lars Gedda, Victor Agmo Hernandez
Summary: This study investigates the effects of polyethylene glycol-(PEG) modified lipids and gangliosides on the Ca2+ induced interaction between liposomes composed of palmitoyl-oleoyl phosphatidylethanolamine (POPE) and palmitoyl-oleoyl phosphatidylserine (POPS) at physiological ionic strength. The results show that naked liposomes tend to adhere, rupture, and collapse on each other's surfaces upon addition of Ca2+, eventually resulting in the formation of large multilamellar aggregates and bilayer sheets. However, the presence of gangliosides or PEGylated lipids leads to the formation of small, long-lived bilayer fragments/disks. PEGylated lipids seem to be more effective than gangliosides at stabilizing these structures. The study suggests that direct liposome-liposome fusion is not the dominating process triggered by Ca2+ in the systems studied.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Saurabh Saraswat, Archana Chugh
Summary: Cell penetrating peptides (CPP) are important tools for intracellular delivery of molecules. In this study, a novel marine-derived CPP from Engraulis japonicus, called Engraulisin, was reported. Engraulisin demonstrated successful cellular uptake and selective antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA), making it a potential candidate for drug delivery.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Emanuela Efodili, Ashlynn Knight, Maryem Mirza, Cedric Briones, Il-Hyung Lee
Summary: This study demonstrates the spontaneous transfer of small membrane-bound peptides between a supported lipid bilayer and giant unilamellar vesicles in vitro. The transfer occurs through the formation of hemi-fusion stalks and is limited to small peptides due to the highly curved structure of the stalk. This system provides a synthetic platform for studying peptide trafficking between synthetic membranes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Niu, Si Jia Chen, Jeffery B. Klauda
Summary: Macrophage membranes in the activated state are more tightly packed, exhibit increased chain order across lipid species, and form specific lipid clusters. These findings provide physiologically accurate models for future computational studies of macrophage membranes and their proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Niki Baccile, Vincent Chaleix, Ingo Hoffmann
Summary: This study measured the bending rigidity of self-assembled structures formed by a new biobased glucolipid bioamphiphile using neutron spin-echo (NSE) technology. The results showed that the bending rigidity of these structures is lower or higher compared to phospholipid membranes, providing a new theoretical basis for the application of these new molecular systems.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Alain Bolano Alvares, Pablo E. A. Rodriguez, Gerardo D. Fidelio
Summary: The behavior of amphiphilic molecules at the air/water interface was studied to evaluate the arrangement formed in a confined area. The surface properties of zwitterionic DPPC lipid and A beta(1-40) amyloid peptide in mixed films were investigated at different temperatures. DPPC undergoes a phase transition depending on temperature and lateral pressure, which allows for the study of its influence on amyloid structure formation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Lukasz Plachta, Marzena Mach, Magdalena Kowalska, Pawel Wydro
Summary: Resveratrol, a popular phytoalexin found in grapes and red wine, has beneficial effects on the cardiovascular system, exhibits antiviral, antibacterial, and antifungal properties, and may have therapeutic effects against cancer. This study investigates the interaction of resveratrol with model cell membranes, demonstrating changes in their physicochemical parameters and highlighting the role of cholesterol content in resveratrol incorporation. The findings suggest that the molecular mechanism of action of resveratrol may involve interactions with lipid rafts.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Edurne Rujas, Beatriz Apellaniz, Johana Torralba, David Andreu, Jose M. M. Caaveiro, Shixia Wang, Shan Lu, Jose L. Nieva
Summary: This study investigates the role of fusion peptide and Trp-rich membrane proximal external region in HIV-1 fusion and demonstrates that liposome-based formulations containing FP-MPER hybrid peptides can induce the production of specific neutralizing antibodies in rabbits. The results support the use of liposomes as vaccine carriers and the inclusion of lipid membranes in immunogens to elicit specific humoral responses.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Dailin Li, Dingyuan Shi, Lei Wang
Summary: G protein-gated inwardly rectifying potassium (GIRK) channels play a significant role in regulating cell excitability. This study investigated the ion permeation mechanism in GIRK2 mutants using molecular dynamic simulations and QM/MM methods. The results revealed the importance of a multi-ion distribution for ion conduction.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Max J. den Uijl, Arnold J. M. Driessen
Summary: Membrane protein insertion into and translocation across the bacterial cytoplasmic membrane are essential processes facilitated by the Sec translocon. The phospholipid dependence of membrane protein insertion has remained mostly unknown. This study reveals that the insertion of the mannitol permease MtlA into the membrane depends on the presence of phosphatidylglycerol and is stimulated by phosphatidylethanolamine.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick Allen, Adam C. Smith, Vernon Benedicto, Abbas Abdulhasan, Vasanthy Narayanaswami, Enrico Tapavicza
Summary: We explore the stability, size, and structure of nanodiscs formed by the N-terminal domain of apolipoprotein E3 and a variable number of 1,2-dimyristoyl-sn-glycero-3-phosphocholine molecules. Our simulations suggest that nanodiscs containing 240 to 420 DMPC molecules are stable. The antiparallel configuration shows more protein-protein interactions and ionic contacts, as well as greater stability and rigidity compared to the parallel configuration.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick M. Keating, Nicholas P. Schifano, Xinrui Wei, Matthew Y. Kong, Jinwoo Lee
Summary: Lassa virus (LASV) infection is dependent on the fusion of its viral membrane with the host cell membrane, and our study reveals that this fusion process involves pH-dependent conformational changes in the transmembrane domain of LASV. These findings provide valuable insights into the fusion mechanism of LASV and can be utilized in the design of therapeutics to combat Lassa virus infections and prevent its potential spread.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Ashley L. Bennett, Kristen N. Cranford, Austin L. Bates, Christopher R. Sabatini, Hee-Seung Lee
Summary: This study employed molecular dynamics simulations to elucidate the binding, folding, and insertion details of TP10W in the cell membrane. The simulations revealed that TP10W can translocate across the lipid membrane as a monomer, and the charged amino acid side chains can move between lipid leaflets. Comparison with point mutated variants demonstrated significant conformational changes due to charge distribution.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Jessica H. van Wonderen, Jason C. Crack, Marcus J. Edwards, Thomas A. Clarke, Gerhard Saalbach, Carlo Martins, Julea N. Butt
Summary: Electrogenic bacteria transfer excess respiratory electrons to metal oxide particles and electrodes through the MtrCAB complex. The crystal structure of MtrCAB from S. baltica OS185 was resolved, and liquid chromatography mass spectrometry was used to determine the mass values of the three proteins in purified MtrCAB complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Review
Biochemistry & Molecular Biology
Yi-Ming Chen, Ching-Tai Lu, Chia-Wen Wang, Wolfgang B. Fischer
Summary: A series of dye ligands were ranked based on docking experiments, selecting the most suitable ligands for binding with different proteins. Additionally, a comparison study was conducted on a series of repurposing drugs and known antivirals.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)