Article
Multidisciplinary Sciences
Marjorie Damian, Maxime Louet, Antoniel Augusto Severo Gomes, Celine M'Kadmi, Severine Denoyelle, Sonia Cantel, Sophie Mary, Paulo M. Bisch, Jean-Alain Fehrentz, Laurent J. Catoire, Nicolas Floquet, Jean-Louis Baneres
Summary: The membrane plays a crucial role in modulating the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific lipid interactions and bulk effects. PIP2 and GM3 induce shifts in the conformational equilibrium of GHSR, favoring G protein activation in different ways.
NATURE COMMUNICATIONS
(2021)
Article
Biophysics
Christopher Pfleger, Jana Kusch, Mahesh Kondapuram, Tina Schwabe, Christian Sattler, Klaus Benndorf, Holger Gohlke
Summary: The opening of HCN channels is controlled by membrane hyperpolarization and the binding of cyclic nucleotides to the CNBD domain. Through a rigidity-theory-based approach, researchers identified different pathways within the CL-CNBD that modulate cAMP-binding responses. Results suggest the presence of functionally relevant submodules within and across structurally discernible subunits in HCN channels.
BIOPHYSICAL JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Quoc Dat Pham, Sofi Nojd, Martin Edman, Katarina Lindell, Daniel Topgaard, Marie Wahlgren
Summary: Mucoadhesion is a common method employed in drug delivery to prolong the contact of drugs with absorption sites and improve drug absorption. By studying the molecular interactions between different polymers and mucin, researchers can gain insights into the mechanisms of how different polymers affect mucin.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Biochemical Research Methods
Wei Wang, Wayne A. Hendrickson
Summary: Hsp70 molecular chaperones play a crucial role in protein disaggregation and folding by binding to ATP and client peptides, with a balance between restraining and stimulating states. New insights have been gained into the Hsp70 chaperone cycle through the discovery of intermediate states and structural plasticity that affect binding interactions.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Luis Fernando Cofas-Vargas, Paola Mendoza-Espinosa, Luis Pablo Avila-Barrientos, Diego Prada-Gracia, Hector Riveros-Rosas, Enrique Garcia-Hernandez
Summary: In addition to its role in ATP production, FOF1-ATP synthase also plays key regulatory functions in the cell membrane. Its dysfunction is associated with various human diseases and poses a threat to the survival of bacterial pathogens. Therefore, FOF1-ATP synthase has become a potential drug target for treating human diseases and combating antibiotic resistance.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Duan Ni, Jiacheng Wei, Xinheng He, Ashfaq Ur Rehman, Xinyi Li, Yuran Qiu, Jun Pu, Shaoyong Lu, Jian Zhang
Summary: Allostery is a direct and efficient method for fine-tuning protein functions, gaining recognition in drug discovery. Identifying allosteric sites is a challenge for drug design, with recent studies revealing bidirectional allosteric coupling and reversed communication between orthosteric and allosteric sites. A new framework combining computational and experimental strategies has been proposed for predicting allosteric sites, demonstrating desirable performance in identifying potential cryptic sites for allosteric drug design.
Article
Chemistry, Medicinal
Zezheng Yang, Nana Zhou, Xukai Jiang, Lushan Wang
Summary: This study investigated the mechanism underlying the differential catalytic activity of TRI101/201 enzymes using structural bioinformatics analysis and molecular dynamics simulation. The findings revealed that the binding stability between trichothecenes and TRI101/201 is dependent on a hydrophobic cage structure within the binding site. An intrinsic disordered loop, termed loop cover, defined the evolutionary patterns of the TRI101/201 protein family. The unique loop displayed different conformations among the subfamilies' structures, impacting the hydrophobic cages. This study provides theoretical support for understanding the catalytic mechanism of TRI101/201 and suggests a direction for rational protein design in the future.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Applied
Saibal Singh, Graham E. Dobereiner
Summary: This study investigates the factors that control the selectivity of internal alkyne hydration using gold(I) catalysts and finds that the choice of solvent influences the selectivity. At ambient temperature, using [(IPr)Au(NCMe)][IMP-H] (C1) as a precatalyst is effective for the hydration of alkyl/alkyl and alkyl/aryl acetylenes.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Biochemical Research Methods
Eunjeong Lee, Jasmina S. Redzic, Elan Zohar Eisenmesser
Summary: Advances in Nuclear Magnetic Resonance (NMR) spectroscopy have allowed for the identification and characterization of movements in enzymes over the last 20 years. The RASSMM approach, based on mutagenesis and NMR, has been developed to help identify and engineer enzyme function. It generates a panel of mutations that can be studied for their catalytic effects and changes to coupled networks.
Article
Chemistry, Multidisciplinary
Carla Calvo-Tusell, Miguel A. Maria-Solano, Silvia Osuna, Ferran Feixas
Summary: This research investigates the allosteric activation mechanisms of IGPS using molecular dynamics simulations, enhanced sampling techniques, and dynamical networks. The simulations reveal how IGPS captures the substrate, forms a closed interface, and creates an oxyanion hole for efficient substrate hydrolysis under the influence of the allosteric effector. The study provides insights into the molecular details of allosteric activation and can guide engineering efforts of IGPS.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
David Scheerer, Bharat V. Adkar, Sanchari Bhattacharyya, Dorit Levy, Marija Iljina, Inbal Riven, Orly Dym, Gilad Haran, Eugene I. Shakhnovich
Summary: Enzymes have a crucial role in controlling chemical reactions and achieving high catalytic efficiency and selectivity. The three-domain enzyme adenylate kinase (AK) catalyzes phosphotransfer between ATP and AMP. Our study using single-molecule FRET spectroscopy reveals that AMP inhibits AK by promoting faster and more cooperative domain closure by ATP, leading to an increased population of the closed state. We developed a model based on experimentally observed opening and closing rates, explaining the complex activity of AK, particularly substrate inhibition, and highlighting the importance of protein motions in enzymatic activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Manuel Sellner, Andre Fischer, Charleen G. Don, Martin Smiesko
Summary: Research using molecular dynamics simulations and protein-protein docking revealed the mechanism of conformational changes between cytochrome P450 enzymes and cytochrome P450 reductase, as well as proposed new conformational transition mechanisms and structural mechanisms for susceptibility to redox states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Giuseppina La Sala, Christopher Pfleger, Helena Kack, Lisa Wissler, Philip Nevin, Kerstin Bohm, Jon Paul Janet, Marianne Schimpl, Christopher J. Stubbs, Marco De Vivo, Christian Tyrchan, Anders Hogner, Holger Gohlke, Andrey I. Frolov
Summary: This study developed a structure-based three-parameter model that integrates local binding site information, coevolution information, and information on dynamic allostery to identify potentially hidden allosteric sites in ensembles of protein structures. The model successfully ranked all known allosteric pockets in the top three positions when tested on five allosteric proteins. Additionally, two novel druggable sites were identified and confirmed in MAT2A and BCKDK protein structures. This model can be used in drug discovery to identify allosteric pockets.
Article
Chemistry, Physical
Filippo Marchetti, Elisabetta Moroni, Alessandro Pandini, Giorgio Colombo
Summary: Allosteric drugs have gained increasing interest, with high-throughput screening being a common practice for their discovery. Despite growing biological information and computational power, challenges remain in selecting allosteric ligands and predicting their impact on target protein function. Computational approaches typically involve molecular docking and molecular dynamics to recover information on the long-range regulation typical of allosteric proteins.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Tanmoy Khan, Nilimesh Das, Kuldeep Singh Negi, Suman Bhowmik, Pratik Sen
Summary: This study investigates the solvation dynamics, conformational fluctuation dynamics, and stability of proteins in deep eutectic solvents (DESs). The results show that the side-chain flexibility and thermal stability of proteins decrease gradually with increasing DES concentration. However, the associated water dynamics only marginally slow down at higher DES concentrations.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Rajni Verma, Jonathan M. Ellis, Katie R. Mitchell-Koch
Summary: YqhD, an enzyme from E. coli, produces valuable bio-renewable fuels and fine chemicals from a broad range of starting materials. The oxidized and reduced states of the NADP/H cofactor binding influence the conformational dynamics of the enzyme, with NADPH-bound monomers having a tighter interdomain space and more rigid cofactor binding compared to NADP-bound monomers. The enzyme's aldehyde reductase activity is enhanced by increased closed conformation sampling during NADPH binding.
Article
Chemistry, Multidisciplinary
Vinod Kumar, Geetha M. Sai, Rajni Verma, Katie R. Mitchell-Koch, Debes Ray, Vinod Kumar Aswal, Prachi Thareja, Ketan Kuperkar, Pratap Bahadur
Summary: In this study, the effects of adding the antioxidant propyl gallate (PG) on the micellization and morphology of aqueous cetyltrimethylammonium bromide (CTAB) solution were investigated using a combination of experimental techniques and molecular dynamics simulations. The results showed that PG can decrease the critical micelle concentration of CTAB and enhance its hydrophobicity, resulting in significant changes in the morphology and structure of CTAB micelles.
Article
Chemistry, Multidisciplinary
Luan C. Doan, Jayangika N. Dahanayake, Katie R. Mitchell-Koch, Abhishek K. Singh, Nguyen Q. Vinh
Summary: Protein dynamics are affected by water molecules, and the dynamics of loosely bound and bulk water differ from the dynamics of water molecules in the tightly bound layer.
Article
Chemistry, Multidisciplinary
Ryan M. Steinert, Micah E. Heikes, Jeremy T. Mitchell-Koch, Gary A. Baker, Katie R. Mitchell-Koch
Summary: Three direct complexometric titration methods and a UV-vis assay were presented for determining bismuth subsalicylate in over-the-counter stomach relief caplets and liquids in student laboratories. These methods are simple, safe, and help students relate real-world sample analysis to theoretical titrimetric concepts.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Chemistry, Physical
Vinod Kumar, Katie R. Mitchell-Koch, Sai Geetha Marapureddy, Rajni Verma, Prachi Thareja, Ketan Kuperkar, Pratap Bahadur
Summary: This study investigates the higher-order micellar transition induced by 1-octanol in an aqueous solution of cetyltrimethylammonium bromide (CTAB), and characterizes its phase behavior, rheology, and scattering properties. The experimental results are validated with computational simulations, providing insights into the solution behavior and molecular interactions.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Subhamay Pramanik, Ryan M. Steinert, Katie R. Mitchell-Koch, Kristin Bowman-James
Summary: Supramolecular macrocyclic forces have been utilized to trap phytate, revealing key interactions at the microenvironment level. The complex chemistry of phytate surrounding the inositol framework has been investigated using crystallographic, theoretical, and solution binding approaches, shedding light on its intramolecular and intermolecular interactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Vinod Kumar, R. Katie Mitchell-Koch, Sai Geetha Marapureddy, Rajni Verma, Prachi Thareja, Ketan Kuperkar, Pratap Bahadur
Summary: This study characterizes the phase behavior, rheology, and small-angle neutron scattering (SANS) of a ternary system consisting of CTAB, C8OH, and water. The results reveal the interesting solution behavior and presence of distinct micelle morphologies in CTAB solutions as a function of C8OH concentration. Computational simulation approaches further validate the experimental findings.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Ryan M. Steinert, Chandana Kasireddy, Micah E. Heikes, Katie R. Mitchell-Koch
Summary: Neutron diffraction and computational characterization were used to identify and study hydrogen bonding interactions involving C delta-H and C epsilon-H in histidine. These interactions play important roles in protein structure and function.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Vinod Kumar, Rajni Verma, Dwarkesh Satodia, Debes Ray, Ketan Kuperkar, Vinod Kumar Aswal, Katie R. Mitchell-Koch, Pratap Bahadur
Summary: The study investigated the self-assembly of three quaternary salt-based cationic surfactants with different polar head groups in aqueous solutions. The presence of BuOH promoted mixed micelle formation, while BTD interfered with micellization. Analyzing the micellar characteristics using various techniques provided insights into micelle size/shape and aggregation number, as well as the morphology transition induced by alcohol addition.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Review
Materials Science, Biomaterials
Jennifer A. Kist, Hua Zhao, Katie R. Mitchell-Koch, Gary A. Baker
Summary: Deep eutectic solvents are gaining attention as potential replacements for traditional organic solvents due to their biodegradability, low toxicity, and cost-effective preparation from widely available natural feedstocks.
JOURNAL OF MATERIALS CHEMISTRY B
(2021)