Review
Pharmacology & Pharmacy
Varun Dewaker, Ashish R. Sharma, Utsab Debnath, Sung Taek Park, Hyeong Su Kim
Summary: This review provides an update on molecular dynamics simulation studies of the TRPV1 channel, focusing on its gating mechanism, ligand-binding sites, and implications for drug design. The article also explores challenges in developing modulators, SAR optimization, and clinical trial studies.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Applied
Zhicheng Wu, Jingbing Xu, Jinggang Ruan, Jiaxin Chen, Xue Li, Yiru Yu, Xinrui Xie, Jie Tang, Dong Zhang, Hongjun Li
Summary: The interaction between myofibrillar proteins (MPs) and capsaicin (CAP) was investigated using multispectral, molecular docking, and molecular dynamics simulation methods. The study found that the resulting complex increased the hydrophobicity of the tryptophan and tyrosine microenvironment as revealed by fluorescence spectral analysis. It was also discovered that the interaction between CAP and MPs was primarily facilitated by hydrogen bonding, van der Waals forces, and hydrophobic interactions, as suggested by molecular docking models and molecular dynamics simulations.
Article
Cell Biology
Ya-Kai Xie, Hao Luo, Shan-Xin Zhang, Xiao-Ying Chen, Ran Guo, Xiao-Yun Qiu, Shuai Liu, Hui Wu, Wen-Bo Chen, Xing-Hua Zhen, Qiang Ma, Jin-Lan Tian, Shun Li, Xinzhong Chen, Qingjian Han, Shumin Duan, Chengyong Shen, Fan Yang, Zhen-Zhong Xu
Summary: This study reveals the mechanisms underlying the development of DNP in patients with diabetes and identifies a potential therapeutic target. The researchers found that GPR177 in A-fiber neurons mediates the secretion of WNT5a, which in turn activates the TRPV1 ion channel and causes pain. These findings contribute to the search for therapies to relieve neuropathic pain.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Physical
Christopher Kang, Rui Sun
Summary: The research indicates that α-synuclein prefers binding to the outer leaflet of synaptic vesicles due to Coulombic interaction, and the association with the membrane facilitates protein folding.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Joanna K. Bujak, Daria Kosmala, Kinga Majchrzak-Kuligowska, Piotr Bednarczyk
Summary: The study confirmed the expression of the TRPV1 ion channel on both mRNA and protein levels in canine PBMC, and indicated that the ion channel is functional.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Dmytro Isaev, Keun-Hang Susan Yang, Waheed Shabbir, Frank Christopher Howarth, Murat Oz
Summary: Capsaicin, a natural alkaloid derived from chili pepper, has various pharmacological effects and can affect cardiovascular function by inhibiting ion currents in cardiac myocytes. Therefore, caution should be exercised when administering capsaicin to individuals with cardiac channelopathies or arrhythmia-prone conditions.
Review
Chemistry, Medicinal
Murat Oz, Dietrich E. Lorke, Frank C. Howarth
Summary: Capsaicin, derived from chili pepper, has various pharmacological actions, including analgesic, anticancer, anti-inflammatory, antiobesity, and antioxidant effects. It acts on not only TRPV1 receptor, but also other ion channels and enzymes. This study categorizes the non-TRPV1 targets of capsaicin and discusses the cellular and molecular mechanisms of its TRPV1-independent effects.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Engineering, Mechanical
Choon-Peng Chng, Yoel Sadovsky, K. Jimmy Hsia, Changjin Huang
Summary: The peroxidation of lipids with polyunsaturated fatty acid tails modulates the biophysical properties of bilayer membrane in a site-specific manner, influencing membrane structure and properties. Specifically, peroxidation at different sites leads to distinct changes in the membrane, with peroxidation in the bilayer interior causing membrane disruption and softening, while peroxidation near the membrane-water interface results in a more ordered and stiffer membrane.
EXTREME MECHANICS LETTERS
(2021)
Article
Physics, Multidisciplinary
Xuegui Lin, Xiaojie Chen, Qing Liang
Summary: The study found that spectrins prefer to interact with phosphatidylethanolamine (PE) lipids, and tend to contact with the liquid-disordered (Ld) domains enriched in unsaturated PE. Anionic lipids enhance the attraction between spectrins and lipid domains, while residue mutation decreases the structural stability of spectrins.
Article
Physics, Multidisciplinary
Lijuan Sun, Yu Cao, Xiaojie Chen, Qing Liang
Summary: The interactions between nanoparticles coated with hydrophilic and hydrophobic ligands and a lipid bilayer were studied using coarse-grained molecular dynamics simulation. The effects of ligand density, ratio of hydrophilic to hydrophobic ligands, and ligand rigidity on the interactions were investigated. The results showed that nanoparticles can either be inserted into or adsorbed on the lipid bilayer depending on their size, ligand ratio, and ligand flexibility. This study provides insights into modulating interactions between amphiphilic nanoparticles and lipid bilayers, and their applications in drug delivery and cell imaging.
COMMUNICATIONS IN THEORETICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Martynas Gavutis, Eric Schulze-Niemand, Hung-Hsun Lee, Bo Liedberg, Matthias Stein, Ramunas Valiokas
Summary: This study combines computational and experimental methods to investigate the fusion of small unilamellar vesicles (SUVs) on mixed self-assembled monolayers (SAMs) with different deuterated tether moieties. Initially, tethered bilayer lipid membrane (tBLM) formation was studied on SAMs with controlled tether surface densities using quartz crystal microbalance with dissipation monitoring (QCM-D). Molecular dynamics simulations were then used to understand the interaction mechanisms between the SUVs and different phases formed by the deuterated tethers. Real-time kinetics were recorded using QCM-D under different osmotic conditions to determine lipid mass accumulation and fusion process. The study reveals the key factors for SUV fusion and tBLM formation on the surfaces, and shows the advantages of the sparsely tethered tBLM system in studying various biophysical phenomena.
Article
Chemistry, Multidisciplinary
Emmanuelle Bignon, Marco Marazzi, Stephanie Grandemange, Antonio Monari
Summary: This study investigates the structural properties of the non-structural protein 6 (Nsp6) of SARS-CoV-2 using long-timescale molecular dynamics simulations and machine learning analysis. The findings reveal the interaction patterns of Nsp6 with the lipid membrane and suggest that the mutation brought by the Omicron variant may alter specific interactions, particularly aiding in anchoring the viral protein to the lipid bilayer interface.
Review
Biotechnology & Applied Microbiology
Ana Emilia Nava-Ochoa, Marilena Antunes-Ricardo, Daniel Guajardo-Flores
Summary: Capsaicinoids in chili peppers not only provide pungency, but also possess beneficial traits such as analgesic and anti-inflammatory properties. Using nano-sized drug delivery systems have been proven to reduce the secondary effects of capsaicinoids while enhancing their bioavailability and absorption.
JOURNAL OF BIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Seong Gi Lim, Sung Eun Seo, Seongjae Jo, Kyung Ho Kim, Lina Kim, Oh Seok Kwon
Summary: In this study, a fast and convenient approach for screening lead vanilloid compounds targeting TRPV1 was proposed. A graphene field-effect transistor with human TRPV1 receptor protein as the bioprobe was fabricated and verified using various analyses. Simulations and experimental analyses confirmed the binding affinity of the ligands with TRPV1.
Article
Chemistry, Physical
Lorena Ruano, Gustavo Cardenas, Juan J. Nogueira
Summary: This study investigates the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers, finding that the permeation of cisplatin through a model membrane involves complex interactions with the polar and non-polar regions of the lipid bilayer, influenced by long-range electrostatic and hydrogen bond interactions. The permeation free-energy profile is determined by a balance between drug/lipid interactions, dehydration of the drug, and changes in membrane ordering along the permeation pathway.
Article
Multidisciplinary Sciences
Gurdeep S. Minhas, Simon Newstead
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biochemistry & Molecular Biology
Joanne L. Parker, Simon Newstead
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Joanne L. Parker, Robin A. Corey, Phillip J. Stansfeld, Simon Newstead
NATURE COMMUNICATIONS
(2019)
Review
Biochemistry & Molecular Biology
Gurdeep S. Minhas, Simon Newstead
BIOCHEMICAL SOCIETY TRANSACTIONS
(2020)
Article
Biochemical Research Methods
Iwan Zimmermann, Pascal Egloff, Cedric A. J. Hutter, Benedikt T. Kuhn, Philipp Brauer, Simon Newstead, Roger J. P. Dawson, Eric R. Geertsma, Markus A. Seeger
Article
Cell Biology
Simon Newstead, Francis Barr
JOURNAL OF CELL SCIENCE
(2020)
Article
Multidisciplinary Sciences
Zhiyi Wu, Simon Newstead, Philip C. Biggin
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Gabriel Kuteyi, Zhiyi Wu, Jiandong Huo, I. David Goldman, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: Folates, also known as vitamin B9, play a critical role in cellular metabolism and their deficiency is linked to various disorders. Mammals cannot synthesize folates and rely on uptake from the diet. The proton-coupled folate transporter is important for folate uptake and drug delivery.
Article
Biochemistry & Molecular Biology
Oliver Adams, Justin C. Deme, Joanne L. Parker, Philip W. Fowler, Susan M. Lea, Simon Newstead
Summary: The structure analysis of Mtb MmpL3 can help us understand the mechanism of drug resistance mutations, revealing the positioning of resistance variants at the drug binding site, and also highlighting a potential alternative route to resistance within the periplasmic domain.
Article
Biology
Andreas Gerondopoulos, Philipp Brauer, Tomoaki Sobajima, Zhiyi Wu, Joanne L. Parker, Philip Biggin, Francis A. Barr, Simon Newstead
Summary: The study investigates the selective retrieval of ER proteins by the KDEL receptor, revealing a dynamic process of signal capture as it enters the binding pocket. Additionally, it uncovers the affinity differences between HDEL and KDEL, attributing the discrepancy to interactions between specific residues at the -4 position of the signal and residues in the receptor binding pocket.
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Zhiyi Wu, Gabriel Kuteyi, Jiandong Huo, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: The proton-coupled solute carriers PepT1 and PepT2 in the SLC15 family are crucial for acquiring dietary nitrogen and have extreme substrate promiscuity. Recent studies on their structure and function provide insights into their potential applications in drug development.
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Dimitrios Kolokouris, Gabriel Kuteyi, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: The study presents the cryo-EM structure of human system xc- in both apo and glutamate bound states, discussing its cystine transport mechanism and highlighting its potential as a target for anticancer therapies due to its role in cellular redox homeostasis. The research shows an allosteric mechanism for ligand discrimination in system xc(-) supported by molecular dynamics and cell-based assays, establishing a mechanism for cystine transport in human cells.
NATURE COMMUNICATIONS
(2021)
Article
Biophysics
Chenghan Li, Zhi Yue, Simon Newstead, Gregory A. Voth
Summary: This study uses multiscale modeling to investigate the functional cycle of proton-coupled peptide transporters (POTs), providing computational confirmation for the alternating access model and a quantitative multiscale kinetic picture of the functioning protein mechanism.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Simon Newstead
Summary: Structural studies on mammalian vitamin transport, especially folates, are lagging behind other metabolites. This study focuses on the three different systems responsible for folate uptake in the human body and the potential of targeting specific folate transporters for developing new antifolates with improved pharmacology. Recent findings on the proton-coupled folate transporter provide insights into antifolate recognition and the mechanism of transport, which, combined with previous knowledge on folate receptors and predictions for the structure of the reduced folate carrier, contribute to the acceleration of antifolate drug development.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joanne L. Parker, Takafumi Kato, Gabriel Kuteyi, Oleg Sitsel, Simon Newstead
Summary: The kidney in mammals maintains blood homeostasis by selectively taking up, retaining or eliminating toxins, drugs and metabolites. Organic anion transporters (OATs) are responsible for recognizing and excreting metabolites and toxins in the nephron. Inhibition of OATs is therapeutically used to enhance drug efficacy and reduce nephrotoxicity. This study presents cryogenic-electron microscopy structures of OAT1 bound to alpha-ketoglutarate, tenofovir, and probenecid, providing molecular insights into alpha-ketoglutarate driven drug elimination and the allosteric regulation of organic anion transport by chloride in the kidney.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)