Article
Pharmacology & Pharmacy
Michael Ramon Lima de Conceicao, Jorge Lucas Teixeira-Fonseca, Leisiane Pereira Marques, Diego Santos Souza, Danilo Roman-Campos
Summary: This study investigated the impact of changes in extracellular pH (pHe) on the pharmacological properties of amiodarone (AMD) in relation to the Na(v)1.5 sodium channel and isolated rat hearts. The results showed that pHe affected the potency of AMD on peak I-Na, as well as its voltage dependence for activation, steady-state inactivation curve, recovery from inactivation, and use-dependent properties. Additionally, AMD caused different changes in the ex vivo ECG profile at different pHe levels.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Jannis Koerner, Simone Albani, Vishal Sudha Bhagavath Eswaran, Anna B. Roehl, Giulia Rossetti, Angelika Lampert
Summary: This article reviews the interaction between local anesthetics and voltage-gated sodium channels, discussing their mechanisms, effects, and specificity, and provides new perspectives for research.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Lina Zhao, Lisa M. Barber, Andrew Hung
Summary: Conotoxins are a family of neurotoxic peptides, with MfVIA being one of them, exhibiting ideal selectivity inhibition on NaV1.8. Molecular dynamics simulations were used to study the effects of various mutations on the structure and dynamics of MfVIA at key residues.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2021)
Article
Biochemistry & Molecular Biology
Eric A. Zizzi, Marco Cavaglia, Jack A. Tuszynski, Marco A. Deriu
Summary: The study investigated the interaction between human tubulin and four volatile anesthetics, predicting binding sites and affinity rankings through docking and Molecular Dynamics simulations. The simulations suggested a transient interaction between anesthetics and microtubules, with interaction strengths consistent with the potencies of the compounds.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Pavel Andrei Montero-Dominguez, Gerardo Corzo
Summary: This study investigates the interaction mechanism between scorpion beta-neurotoxins and the human sodium channel. Computational techniques were used to reveal that the toxins bind to specific regions of the sodium channel, leading to voltage sensor entrapment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Bin Liu, Xiaoli Fu, Yuhui Du, Zichen Feng, Xiaoxue Liu, Zhiyuan Li, Fangfang Yu, Guoyu Zhou, Yue Ba
Summary: In this study, the potential mechanisms of 35 ferroptosis-related genes in U87 glial cells exposed to fluoride were explored using bioinformatics methods. Ten pivotal genes were identified, and 10 possible drugs for fluorosis were predicted and screened. Molecular docking and simulation results suggested that Celestrol and LDN-193189 may be effective candidate drugs for the treatment of fluorosis by targeting ferroptosis-related genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ada Y. Chen, Bernard R. Brooks, Ana Damjanovic
Summary: In bacterial voltage-gated sodium channels, the passage of ions through the pore is controlled by a selectivity filter (SF) composed of four glutamate residues. This study proposes an alternative mechanism for selectivity, based on ion-triggered shifts in pKa values of SF glutamates. The mechanism suggests that selectivity is achieved through ion-triggered shifts in the protonation state, favoring more conductive states for Na+ ions and less conductive states for K+ ions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Fortunatus C. Ezebuo, Ikemefuna C. Uzochukwu
Summary: Schistosomiasis is a neglected disease with significant health impact in tropical and subtropical regions. Current treatment options using praziquantel or oxamniquine have limitations due to resistance or tolerance. This study used molecular docking and dynamics simulations to predict potential antischistosomal drugs, with tolmetin and diflunisal showing promising binding energies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Pharmacology & Pharmacy
Masakazu Kotoda, Toru Matsuoka, Keiichi Wada, Selwyn Jayakar, Hirofumi Ino, Koji Kawago, Yasutomo Kumakura
Summary: This study investigated the potential of amiodarone, a multiple channel blocker, as a long-lasting local anesthetic and analgesic. It was found that amiodarone produced robust anesthesia and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade without affecting motor blockade. Low-dose amiodarone was also effective in relieving inflammatory pain without the need for capsaicin co-administration. Furthermore, local amiodarone did not cause any cardiovascular or central nervous system side effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Archisha Prakash, Subhomoi Borkotoky, Vikash Kumar Dubey
Summary: Before the rise of SARS-CoV-2, the emergence of other coronaviruses has alerted researchers to the possibility of future novel pathogens. In this study, the researchers focused on identifying inhibitors that target the main protease of coronaviruses, which plays a critical role in their life cycle. Using computational methods, they screened FDA-approved drugs and found three potential inhibitors that can target both the monomeric and dimeric sites of the main protease. These compounds show stable behavior in simulations and have equal binding capacity for both targeted sites, suggesting their potential as inhibitors against SARS-CoV-2 main protease.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Physical
Juan Cai, Rongwei Shi
Summary: This study investigates the detailed interaction between first-generation antifungal agents (miconazole, fluconazole, and voriconazole) and CYP2C9 using docking and molecular dynamics simulation methods. The results show that miconazole has the highest binding affinity compared to fluconazole and voriconazole. Interestingly, water molecules play a significant role in regulating the binding of miconazole to the protein.
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2023)
Article
Immunology
Manoj Kumar Yadav, Manish Kumar Tripathi, Srishti Yadav
Summary: Plasmodium knowlesi, the least studied malaria parasite in Southeast Asia, is characterized as a significant cause of morbidity and mortality. This study identifies PkDHFR as a drug target and explores inhibitors to combat resistance, providing potential candidates for treating P. knowlesi malaria.
MICROBIAL PATHOGENESIS
(2021)
Article
Pharmacology & Pharmacy
Julie I. R. Labau, Matthew Alsaloum, Mark Estacion, Brian Tanaka, Fadia B. Dib-Hajj, Giuseppe Lauria, Hubert J. M. Smeets, Catharina G. Faber, Sulayman Dib-Hajj, Stephen G. Waxman
Summary: Lacosamide, commonly used as an anti-epileptic drug for pain treatment, differs from other drugs in its mechanism of action. The W1538 residue and intact local anesthetic binding site are crucial for lacosamide to block Na(V)1.7 channels at clinically-achievable concentrations.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Agricultural Engineering
Francisco Thalysson Tavares Cavalcante, Aluisio Marques da Fonseca, Jeferson Yves Nunes Holanda Alexandre, Jose C. S. dos Santos
Summary: Biolubricants derived from renewable raw materials and synthesized using enzymes have gained market attention. This study focuses on the synthesis reactions of biolubricants using the genetically-modified lipase Eversa (R) Transform 2.0. Computational tools, such as docking and molecular dynamics, were employed to understand the interactions and stability of enzyme-ligand complexes. In vitro validation confirmed the improved esterification activity of the lipase with isoamyl alcohol, suggesting its potential in the biolubricant production system.
INDUSTRIAL CROPS AND PRODUCTS
(2022)
Article
Biochemistry & Molecular Biology
Biswajit Naik, Nidhi Gupta, Priya Godara, Varshita Srivastava, Prateek Kumar, Rajanish Giri, Vijay Kumar Prajapati, Kailash C. Pandey, Dhaneswar Prusty
Summary: Compared to last year, there has been a significant increase in malaria cases in 2021. The emergence of drug-resistant strains of the malaria parasite Plasmodium falciparum has reduced the effectiveness of current antimalarial drugs. To address this issue, researchers aimed to identify natural compounds that can inhibit multiple validated drug targets of Plasmodium falciparum. Screening of natural compounds from the NPASS database led to the identification of 20 compounds with promising potential. Molecular simulations confirmed the stable binding affinity of six of these compounds, indicating their potential as future antimalarial drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pharmacology & Pharmacy
Kiran George, Diego Lopez-Mateos, Tarek Mohamed Abd El-Aziz, Yucheng Xiao, Jake Kline, Hong Bao, Syed Raza, James D. Stockand, Theodore R. Cummins, Luca Fornelli, Matthew P. Rowe, Vladimir Yarov-Yarovoy, Ashlee H. Rowe
Summary: This study investigates the gating mechanism of voltage-gated sodium channel Na(V)1.8 and identifies a toxin, NaTx36, produced by Arizona bark scorpions, which can inhibit Na(V)1.8 currents and block pain signals. Mutagenesis experiments reveal critical amino acids involved in the inhibitory effects of NaTx36. Computational modeling provides insights into the interaction between the toxin and the channel.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yuliet Mazola, Jose C. E. Marquez Montesinos, David Ramirez, Leandro Zuniga, Niels Decher, Ursula Ravens, Vladimir Yarov-Yarovoy, Wendy Gonzalez
Summary: Atrial fibrillation is a common cardiac arrhythmia with limited treatment options. This study focuses on the structural similarities of cardiac ion channels to explore multi-target selective drugs for AF treatment.
Article
Pharmacology & Pharmacy
Jan Maly, Aiyana M. Emigh, Kevin R. DeMarco, Kazuharu Furutani, Jon T. Sack, Colleen E. Clancy, Igor Vorobyov, Vladimir Yarov-Yarovoy
Summary: The voltage-gated potassium channel hERG plays a crucial role in membrane repolarization of cardiac myocytes. By using Rosetta modeling, researchers investigated the conformational changes and drug binding mechanisms associated with hERG channel inactivation. The study provides insights into the structural changes and ligand interactions of hERG in the inactivated state.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Diego Lopez Mateos, Vladimir Yarov-Yarovoy
Summary: Voltage-gated ion channels are crucial for action potential generation and propagation. Peptidic toxins from animal venoms can target these channels and be used as scaffolds for designing new channel modulators. However, determining the structures of peptide toxins bound to ion channels in physiologically relevant states remains challenging.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biology
Phuong T. Nguyen, Hai M. Nguyen, Karen M. Wagner, Robert G. Stewart, Vikrant Singh, Parashar Thapa, Yi-Je Chen, Mark W. Lillya, Anh Tuan Ton, Richard Kondo, Andre Ghetti, Michael W. Pennington, Bruce Hammock, Theanne N. Griffith, Jon T. Sack, Heike Wulff, Vladimir Yarov-Yarovoy
Summary: This study successfully designed peptide inhibitors of human Na(V)1.7 channels using available structural and experimental data. These inhibitors showed high selectivity and efficacy, and have the potential to be used as a new class of biologics for pain therapy.
Article
Biology
Flavia P. Franco, Pingxi Xu, Brandon J. Harris, Vladimir Yarov-Yarovoy, Walter S. Leal
Summary: The southern house mosquito uses two odorant receptors, CquiOR10 and CquiOR2, to detect oviposition attractants skatole and indole. Through mutation experiments and structural modeling, it was found that a single amino acid substitution can alter the specificity of the receptors, leading to finely tuned volumetric space to accommodate specific oviposition attractants.
Article
Medicine, Research & Experimental
Lu Ren, Phung N. Thai, Raghavender Reddy Gopireddy, Valeriy Timofeyev, Hannah A. Ledford, Ryan L. Woltz, Seojin Park, Jose L. Puglisi, Claudia M. Moreno, Luis Fernando Santana, Alana C. Conti, Michael I. Kotlikoff, Yang Kevin Xiang, Vladimir Yarov-Yarovoy, Manuela Zaccolo, Xiao-Dong Zhang, Ebenezer N. Yamoah, Manuel F. Navedo, Nipavan Chiamvimonvat
Summary: Sinoatrial node (SAN) cells express a diverse repertoire of adenylyl cyclases (ACs), with ACI as the predominant Ca2+-activated isoform. ACI plays a role in sustaining the rise of local cAMP and heart rates by forming functional microdomains with HCN4 channels. Downregulation of ACI gene also leads to sinus node dysfunction.
Meeting Abstract
Biophysics
Yanxiao Han, Gonzalo Hernandez-Hernandez, Pei-Chi Yang, John R. D. Dawson, Kevin R. DeMarco, Kyle C. Rouen, Khoa Ngo, Slava Bekker, Vladimir Yarov-Yarovoy, Colleen E. Clancy, Igor V. Vorobyov
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Brandon J. Harris, Phuong T. Nguyen, Vladimir Yarov-Yarovoy
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Diego Lopez Mateos, Vladimir Yarov-Yarovoy
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Khoa Ngo, Kyle C. Rouen, John R. D. Dawson, Aiyana M. Emigh Cortez, Diego Lopez Mateos, Jan Maly, Kevin DeMarco, Vladimir Yarov-Yarovoy, Igor Vorobyov, Colleen E. Clancy
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Khoa Ngo, Diego Lopez Mateos, Yanxiao Han, Vladimir Yarov-Yarovoy, Igor Vorobyov, Colleen E. Clancy
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Aiyana Emigh Cortez, Kevin DeMarco, Kazuharu Furutani, Jon T. Sack, Colleen E. Clancy, Igor V. Vorobyov, Vladimir Yarov-Yarovoy
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Kyle C. Rouen, Khoa Ngo, Abhishek A. Kognole, John R. D. Dawson, Borislava Bekker, Vladimir Yarov-Yarovoy, Alexander D. MacKerell, Igor Vorobyov
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Ryan L. Woltz, Adith Srivatsa, Kevin DeMarco, Diego Lopez Mateos, Phuong T. Nguyen, Xiao-Dong Zhang, Igor V. Vorobyov, Vladimir Yarov-Yarovoy, Nipavan Chiamvimonvat
BIOPHYSICAL JOURNAL
(2022)