Article
Ecology
Divya Lakshmanan Mangalath, Shabeer Ali Hassan Mohammed
Summary: This study explores the low specificity and high responsiveness of estrogen hormone receptors (ERs) towards chemically distinct exogenous substances, suggesting a possible environmental regulation of ERs and common structural features with prokaryotic taxis receptors. Despite sharing common domain structural folds and common ligand-based pharmacophore features, a significant sequence divergence is observed between bacterial chemotaxis receptors and human ERs, indicating a conservation of protein architecture for specific function regardless of sequence identity.
FRONTIERS IN ECOLOGY AND EVOLUTION
(2021)
Review
Endocrinology & Metabolism
Sabine Richard, Juan Ren, Frederic Flamant
Summary: Thyroid hormone signaling is important for brain development, particularly for the maturation of GABAergic neurons. Research has focused on understanding the mechanisms by which TH affects GABAergic neurons and the challenges of gene expression studies in this field. Understanding the actions of TH in the developing brain could lead to advancements in the prevention and treatment of neurological disorders.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Physical
Jianhua Wu, Yu Zhou, Jilong Zhang, Hong-Xing Zhang, Ran Jia
Summary: This study utilized molecular dynamics simulations to reveal the key residues and binding process of the protein-protein interaction between EphA6 and Odin proteins, providing an in-depth understanding of protein-protein interactions. The agreement between experimental and calculated values offers theoretical guidance for protein drug design.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Endocrinology & Metabolism
Sonia Verma, Soumyananda Chakraborti, Om P. Singh, Veena Pande, Rajnikant Dixit, Amit V. Pandey, Kailash C. Pandey
Summary: This study conducted a systematic analysis of the LBD of the THR-like family, identified key residues, and studied their conservation, providing important insights into the roles of these residues in drug, ligand, and protein-protein interactions.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Chemistry, Medicinal
Sreekanth Rajan, Ho Sup Yoon
Summary: Nuclear receptors (NRs) are ligand-induced transcriptional factors that regulate gene expression by binding to ligands. Some ligands form covalent bonds with NRs. Conserved cysteines in specific regions of NRs play a key role in the covalent attachment. These structural insights aid drug discovery efforts targeting NRs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Giulia D'Arrigo, Ida Autiero, Eleonora Gianquinto, Lydia Siragusa, Massimo Baroni, Gabriele Cruciani, Francesca Spyrakis
Summary: Nuclear receptors (NRs) are transcription factors that play an important role in multiple diseases and their intrinsic dynamics make them a challenging target in drug discovery. This study proposes a methodology based on the computation and comparison of protein cavities in NR structures to uncover their dynamic profile. This approach can guide research on NR intrinsic dynamics, aid in selecting reference structures for drug design, and facilitate the identification of alternative binding sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Hamid Reza Kalhor, Elham Taghikhani
Summary: The study investigated the effect of commonly used drugs on the release of warfarin bound to HSA in silico. Both s-ibuprofen and ascorbic acid were found to exhibit allosteric effects on the release of warfarin from HSA, with ibuprofen showing a stabilizing effect and ascorbic acid aiding in the release through destabilization of HSA. Molecular dynamics simulations provided valuable insights into the interactions of drugs with the protein and the mechanism of anticoagulant release.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Namita Dube, Sabab Hasan Khan, Riley Sasse, C. Denise Okafor
Summary: Allosteric pathways in proteins involve networks of amino acid residues that transmit signals between distant sites. This study uses molecular dynamics simulations and suboptimal path analysis to discover new allosteric networks in steroid receptors, focusing on evolutionarily conserved pathways. The researchers identify a conserved network connecting a predicted allosteric site between helices 9 and 10 of the ligand-binding domain to the activation function surface 2 (AF-2). The study suggests the evolutionary importance of this site in steroid receptors and provides an approach to discover previously unknown allosteric sites in proteins.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Namita Dube, Sabab Hasan Khan, Riley Sasse, C. Denise Okafor
Summary: Allosteric pathways in proteins allow for the transmission of signals between distant sites through inter-residue interactions. This study utilizes molecular dynamics simulations and suboptimal path analysis to identify new allosteric networks in steroid receptors, focusing on evolutionarily conserved pathways. The investigation reveals a conserved network connecting a predicted allosteric site located between helices 9 and 10 of the ligand-binding domain to the activation function surface 2 (AF-2). The importance of this site is highlighted by its presence in a region characterized by conserved inter-residue contacts.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Plant Sciences
Ruphi Naz, Andleeb Khan, Badrah S. Alghamdi, Ghulam Md Ashraf, Maimonah Alghanmi, Altaf Ahmad, Sheikh Shanawaz Bashir, Qazi Mohd Rizwanul Haq
Summary: Ionotropic glutamate receptors (iGluRs) play an important role in neurons, with involvement in memory, neuronal development, and synaptic plasticity. Arabidopsis thaliana has genes comparable to human iGluRs, affecting plant growth and physiological activities. The evolutionary relationship between animal and plant glutamate receptors suggests a correlation, which can be utilized for early detection of neurodegenerative diseases. This review updates knowledge on Arabidopsis glutamate receptors, their evolution, functions, and expression, in comparison with iGluRs. Additionally, the use of FRET nanosensors for understanding neurotransmitter signaling via glutamate receptors in animals and plants is discussed.
Article
Chemistry, Medicinal
Simone Schierle, Apirat Chaikuad, Felix F. Lillich, Xiaomin Ni, Stefano Woltersdorf, Espen Schallmayer, Beatrice Renelt, Riccardo Ronchetti, Stefan Knapp, Ewgenij Proschak, Daniel Merk
Summary: RXR serves as universal heterodimer partners for nuclear receptors, showing high therapeutic potential but limited by current agonists. Development of new RXR ligands based on oxaprozin led to optimized compounds with improved in vivo properties and high selectivity for RXR activation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Plant Sciences
Courtney E. Dresden, Quratulayn Ashraf, Aman Y. Husbands
Summary: The StARkin domain is an evolutionarily conserved structure with a deep hydrophobic pocket capable of binding lipophilic ligands. Dysregulation of StARkin proteins has significant effects on disease and development. Recent studies highlight the diversity of regulatory mechanisms employed by the StARkin module, providing valuable insights for researchers.
CURRENT OPINION IN PLANT BIOLOGY
(2021)
Article
Environmental Sciences
Wei Wang, Qiyao Ma, Xinliang Ding, Yihua Xu, Mengting He, Jie Xu, Jianjun Liu, Cheng Ji, Jie Zhang
Summary: This study found that exposure to Bromoacetamide (BAcAm) can cause developmental toxicity in zebrafish embryos, possibly by disrupting thyroid hormone homeostasis.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Endocrinology & Metabolism
Rutchanna M. S. Jongejan, Marcel E. Meima, W. Edward Visser, Tim I. M. Korevaar, Sjoerd A. A. van den Berg, Robin P. Peeters, Yolanda B. de Rijke
Summary: This study determined the distribution and binding affinity of thyroid hormone metabolites to thyroid hormone distributor proteins, and found that the distribution of metabolites differs from that of thyroid hormones. This has potential clinical importance for the interpretation of thyroid hormone metabolism.
Article
Chemistry, Physical
Zhaoqian Su, Kalyani Dhusia, Yinghao Wu
Summary: The binding of cell surface receptors with their extracellular ligands initiates various intracellular signaling pathways, but our understanding of the cellular functions of these receptors is limited. Membrane undulations negatively affect ligand-receptor interactions, and the preassembly of membrane receptors can accelerate ligand binding kinetics and reduce noise during the process. These findings underscore the importance of membrane environments in regulating the function of membrane receptors and suggest potential applications of the simulation method in specific receptor systems involved in cell signaling.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Review
Chemistry, Multidisciplinary
Siewert J. Marrink, Luca Monticelli, Manuel N. Melo, Riccardo Alessandri, D. Peter Tieleman, Paulo C. T. Souza
Summary: The Martini model is a coarse-grained force field for molecular dynamics simulations that has been developed and refined over nearly two decades. Its popularity stems from its systematic and intuitive building-block approach, as well as its open development and continuous validation. The model's easy implementation in the widely used Gromacs software suite has also contributed to its popularity.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Article
Cell Biology
Adriano de Freitas Fernandes, Diego Antonio Leonardo, Italo Augusto Cavini, Higor Vinicius Dias Rosa, Jhon Antoni Vargas, Humberto D'Muniz Pereira, Alessandro S. Nascimento, Richard Charles Garratt
Summary: This study reports the crystal structure of the heterodimer formed between Sep1 and Sep2 from fruit fly, which is the first insect septin to be described. The structure shows similarities to human septins, including individual amino acid interactions. Molecular dynamics simulations revealed the mechanism of dimer dissociation. These findings contribute to a better understanding of septin assembly and disassembly.
Article
Biochemistry & Molecular Biology
Rosa L. Cordeiro, Camila R. Santos, Mariane N. Domingues, Tatiani B. Lima, Renan A. S. Pirolla, Mariana A. B. Morais, Felippe M. Colombari, Renan Y. Miyamoto, Gabriela F. Persinoti, Antonio C. Borges, Marcelo A. de Farias, Fabiane Stoffel, Chao Li, Fabio C. Gozzo, Marin van Heel, Marcelo E. Guerin, Eric J. Sundberg, Lai-Xi Wang, Rodrigo V. Portugal, Priscila O. Giuseppe, Mario T. Murakami
Summary: This study elucidated the key biochemical steps and molecular mechanisms by which Bifidobacterium longum utilizes high-mannose N-glycans, providing insights into the utilization of this perennial carbon and energy source in the intestinal lumen.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Barbora Waclawikova, Paulo Cesar Telles de Souza, Markus Schwalbe, Constantinos G. Neochoritis, Warner Hoornenborg, Sieger A. Nelemans, Siewert J. Marrink, Sahar El Aidy
Summary: The gut-bacterial metabolite 5-hydroxyindole has been found to stimulate intestinal motility and can serve as a potential therapeutic for gastrointestinal motility disorders such as constipation. Oral administration of 5-hydroxyindole has minimal effects on the rat cecal microbiota. Molecular dynamics simulations suggest potential-binding pockets of 5-hydroxyindole in the L-type voltage-gated calcium channels, which have been associated with gastrointestinal motility disorders.
Article
Biophysics
Justin L. MacCallum, Shangnong Hu, Stefan Lenz, Paulo C. T. Souza, Valentina Corradi, D. Peter Tieleman
Summary: We present a complete implementation of Martini 2 and Martini 3 in OpenMM, a flexible molecular dynamics package. This implementation allows for Martini simulations using the unique features of both Martini and OpenMM. We provide a GitHub repository for testing, compare accuracy and performance with GROMACS, and discuss limitations and potential solutions.
BIOPHYSICAL JOURNAL
(2023)
Article
Biology
Joao Victor de Souza, Victor H. R. Nogueira, Alessandro S. Nascimento
Summary: The correct evaluation of ligand binding free energies by computational methods is still a challenging research area. Four main categories of methods, including molecular docking, thermodynamic ensembles, alchemical methods, and biased simulations, are commonly used for these calculations. In this study, the Monte Carlo Recursion (MCR) method is introduced as an intermediate approach for ligand binding evaluation, showing good correlation with experimental data and providing insights into the binding energy funnel.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Charly Empereur-mot, Kasper B. Pedersen, Riccardo Capelli, Martina Crippa, Cristina Caruso, Mattia Perrone, Paulo C. T. Souza, Siewert J. Marrink, Giovanni M. Pavan
Summary: By using the SwarmCG automatic multiobjective optimization approach, we have successfully refined the bonded interaction parameters in the Martini coarse-grained force field (CG FF) lipid models. Through experimental observables and all-atom molecular dynamics simulations, we optimized 80 model parameters and obtained improved and transferable Martini lipid models.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Amita R. Sahoo, Paulo C. T. Souza, Zhiyuan Meng, Matthias Buck
Summary: The structures and dynamics of transmembrane (TM) receptor regions play a crucial role in understanding how signaling occurs across membranes. In this study, the configurations of TM region dimers were investigated using CG molecular dynamics simulations with the Martini 3 force field. The results showed a reasonable agreement with ab initio predictions and NMR-derived structures, with some differences observed between the different prediction methods. The implications of these findings for transmembrane signaling and peptide-based pharmaceutical development are discussed.
Article
Biochemistry & Molecular Biology
Mariana T. Q. de Magalhaes, Talita Stelling de Araujo, Bruno Marques Silva, Luis Pena Icart, Sandra M. N. Scapin, Marcius da Silva Almeida, Luis Mauricio T. R. Lima
Summary: This study investigated the impact of sequence variations between two variants of E. coli L-asparaginase (EcA2) on their biological function, stability, and interchangeability. Results showed that although these two enzymes had similar specific activity in vitro, they exhibited different behavior in vivo. Further analysis revealed that the amino acid differences between the two variants led to conformational changes, affecting surface accessibility and susceptibility to proteolysis.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Fernando de Sa Ribeiro, Luis Mauricio T. R. Lima
Summary: The crystallographic B-factor, a surrogate for local protein flexibility, was investigated for its thermal dependence and correlation with protein conformational changes. The exponential thermal dependence of the B-factor was found to be similar for all atoms, suggesting that thermal vibration of the atom does not necessarily correlate with protein conformational dynamics.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Gilberto P. Pereira, Brian Jimenez-Garcia, Riccardo Pellarin, Guillaume Launay, Sangwook Wu, Juliette Martin, Paulo C. T. Souza
Summary: Proteolysis targeting chimeras (PROTACs) are emerging as a promising therapeutic approach for cancer treatment. This study presents a computational method that combines docking, energy scoring, and solvent-accessible surface distance filtering to generate PROTAC-compatible protein-protein interaction interfaces even in the absence of known PROTAC ligands.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Chemistry, Physical
Luis Borges-Araujo, Ilias Patmanidis, Akhil P. Singh, Lucianna H. S. Santos, Adam K. Sieradzan, Stefano Vanni, Cezary Czaplewski, Sergio Pantano, Wataru Shinoda, Luca Monticelli, Adam Liwo, Siewert J. Marrink, Paulo C. T. Souza
Summary: In this review, the authors provide an overview of pragmatic coarse-grained (CG) protein models, which combine physics-based implementation and top-down experimental approaches for parameterization. These CG models, with most protein residues represented by at least two beads, allow for some degree of chemical specificity. The review includes discussions on recent applications and future perspectives in the field.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Luis Borges-Araujo, Ana C. Borges-Araujo, Tugba Nur Ozturk, Daniel P. Ramirez-Echemendia, Balazs Fabian, Timothy S. Carpenter, Sebastian Thallmair, Jonathan Barnoud, Helgi I. Ingolfsson, Gerhard Hummer, D. Peter Tieleman, Siewert J. Marrink, Paulo C. T. Souza, Manuel N. Melo
Summary: Cholesterol plays a crucial role in biomembranes by regulating various properties of lipid bilayers. Martini 3 model offers significant improvements in interaction balance and molecular packing, and includes a new cholesterol model that mitigates some limitations of its predecessor.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Materials Science, Biomaterials
Amadeus C. S. de Alcantara, Levi C. Felix, Douglas S. Galvao, Paulo Sollero, Munir S. Skaf
Summary: Bones play vital roles in providing support and facilitating motion for animals. The relationship between structure and mechanical properties in bones is still not fully understood. This study investigates the structural and mechanical properties of bone molecular models composed of collagen, hydroxyapatite, and water. The results show that high mineral content makes bones stiffer, and water content also significantly affects the mechanical properties of bones.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Chemistry, Physical
Kai Steffen Stroh, Paulo C. T. Souza, Luca Monticelli, Herre Jelger Risselada
Summary: This study utilizes mixed-variable particle swarm optimization to automatically parameterize molecules within the Martini 3 coarse-grained force field, matching both structural and thermodynamic data. The approach optimizes both bonded and nonbonded interactions while maintaining the search efficiency of vector guided particle swarm optimization methods. Additionally, noise-mitigation strategies are explored for matching the phase-transition temperatures of lipid membranes.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)