Article
Biochemistry & Molecular Biology
Alexandra V. Krivitskaya, Maria G. Khrenova
Summary: Penicillin-binding proteins 2 (PBP2) are important enzymes in bacterial cell wall formation and their inhibition is used in treating various diseases. Resistance to the drug ceftriaxone, used for gonorrhea treatment, has increased in PBP2, posing a threat. The study uncovers the inhibition mechanism of ceftriaxone on PBP2 from wild-type and mutant strains of Neisseria Gonorrhoeae. The findings reveal differences in the reaction steps and dynamics, as well as the impact on drug binding affinity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Qi Xin, Wenying Zhang, Shuai Yuan
Summary: In this study, the intermediate structures of ChR2 in the photocycle were modeled and molecular dynamics simulations were performed to understand the mechanism of ion channel opening. The results show that the structural models of the intermediates are reasonable and the ion channel is open in the P520 state.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Si-Yuen Lee, Julian George, David Nagel, Hua Ye, Leonard Seymour
Summary: This study proposed a 3D platform based on RGD-alginate for encapsulating optogenetically modified human neuronal cells, demonstrating their survival and ability to express functional neurons.
Article
Biochemistry & Molecular Biology
Phujinn Honorio, Supawadee Sainimnuan, Supa Hannongbua, Patchreenart Saparpakorn
Summary: The research discovered that protoberberine alkaloids isolated from natural resources are potent inhibitors of acetylcholinesterase (AChE) and have the potential to reduce symptoms of Alzheimer's disease. The key interactions of palmatine and berberine with AChE were identified as 7C-7C interactions with specific amino acids and H-bond interactions. In contrast, cyclanoline showed a different binding mode and preference for a deeper site within AChE.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Bella Grigorenko, Tatiana Domratcheva, Alexander Nemukhin
Summary: The oxygenase activity of the flavin-dependent enzyme RutA is associated with the formation of flavin-oxygen adducts in the enzyme active site. Using quantum mechanics/molecular mechanics (QM/MM) modeling, we investigated potential reaction pathways initiated by triplet state complexes of molecular oxygen with reduced flavin mononucleotide (FMN) in protein cavities. The results show that these complexes can be located at different positions on the isoalloxazine ring of flavin, and the activated dioxygen attacks specific positions in the ring, resulting in covalent adducts or direct oxidation of flavin.
Article
Biochemistry & Molecular Biology
Mohsen Sargolzaei, Hossein Nikoofard
Summary: In this study, we designed a suitable ester prodrug of omapatrilat for CNS diseases by considering its ability to penetrate the blood-brain barrier. The most potent stereoisomers against brain carboxylesterase were determined through molecular docking and homology modeling. Molecular dynamics simulation and structural analysis were performed to confirm the suitability of the prodrug structure for crossing the blood-brain barrier and binding to brain carboxylesterase. Additionally, the QM/MM calculation revealed the catalytic reaction mechanism of the prodrug against brain carboxylesterase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Physical
Marvin Asido, Rajiv K. Kar, Clara Nassrin Kriebel, Markus Braun, Clemens Glaubitz, Igor Schapiro, Josef Wachtveitl
Summary: A transient near-UV absorption signature was identified in Krokinobacter eikastus rhodopsin 2 (KR2) which could serve as a marker for retinal configuration. Hybrid quantum mechanics/molecular mechanics simulations revealed that this signature corresponds to S-0 -> S-3 and/or S-0 -> S-5 transitions, and these transitions show negligible spectral shift with changes in the protein environment. The study also explored potential optogenetic applications through near-UV quenching experiments, demonstrating ultrafast regeneration of the parent state of KR2.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Raul Alvarado, Gustavo Cardenas, Juan J. Nogueira, Nicolas Ramos-Berdullas, Marcos Mandado
Summary: This study simulated the permeation of dioxin-like pollutants through lipid membranes using CMD and umbrella sampling. The results showed that TCDD and TCDF reached energy minima at distances of 8 angstrom and 9.5 angstrom from the centre of the membrane, respectively. The interactions between the molecules and the lipid membrane were mainly governed by dispersion forces, independent of the toxicity of the molecules.
Review
Oncology
Tianyu Terry Gao, Teak-Jung Oh, Kritika Mehta, Yu-En Andrew Huang, Tyler Camp, Huaxun Fan, Jeong Won Han, Collin Michael Barnes, Kai Zhang
Summary: Opsin-based optogenetics, a powerful biomedical tool, utilizes light to control protein conformation. It has been used to control ion flow across cell membranes, allowing precise control of action potential in excitable cells. With advancements, it can also control gene expression and signal transduction, offering insights into health and diseases. Its clinical potential, especially in blindness treatment, has been recognized.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Physical
Gustavo Cardenas, Vincent Ledentu, Miquel Huix-Rotllant, Massimo Olivucci, Nicolas Ferre
Summary: The ARM+MEM protocol incorporates all relevant protonation microstates to provide a more accurate modeling of rhodopsins' absorption spectrum. By simulation on a toy model and Anabaenasensory rhodopsin, it is confirmed that considering multiple microstates improves the description of the absorption spectrum.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Article
Chemistry, Medicinal
Emmanuelle Bignon, Antonio Monari
Summary: This article investigates the RNA genome replication mechanism of the SARS-CoV-2 virus. Through calculations and simulations, the high efficiency of the viral polymerase and the unique active site of the enzyme are discovered. The results contribute to the future design of antiviral drugs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Dmitry P. Kapusta, Fedor D. Mulashkin, Maria G. Khrenova
Summary: Using QM/MM potentials, molecular dynamics simulations were conducted to study the tautomerization between keto, cis- and trans-enol forms of DMHI. It was found that the keto form is the most stable, followed by the cis-enol form, while the trans-enol form is higher in energy. The presence of two absorption bands in the experimental absorption spectrum of DMHI in water solution was attributed to the cis-enol and keto forms of the chromophore based on calculated excitation energies.
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Christina Eleftheria Tzeliou, Markella Aliki Mermigki, Demeter Tzeli
Summary: The multiscaling quantum mechanics/molecular mechanics (QM/MM) approach is a powerful tool for investigating chemical reactions' mechanisms, drug delivery, molecular devices properties, etc. This review briefly discusses the main methodologies in multiscaling approaches and provides a review on calculations and reactions on metalloproteins.
Article
Cell & Tissue Engineering
Alexander R. Ochs, Patrick M. Boyle
Summary: Computational simulations suggest that subthreshold optogenetic stimulation can modulate the propensity for EADs and EAD-associated ectopic beats. At the cell-scale, GtACR1 reduces, while ChR2 increases, EAD incidence; at the organ-scale, these optogenetic stimulations can suppress or provoke EAD-associated ectopic beats in ventricular models. Validation in animal models may lead to novel anti-arrhythmia treatments.
CELLULAR AND MOLECULAR BIOENGINEERING
(2023)
Article
Chemistry, Applied
Sulejman Skoko, Cosimo Micheletti, Emanuele Grifoni, Franco Egidi, Tommaso Giovannini, Andrea Pucci, Chiara Cappelli
Summary: We propose a synergistic computational/experimental investigation of fluorescence spectra in aqueous solution. We develop a reliable and cost-effective computational protocol that accurately describes the solute-solvent interactions and takes into account both specific hydrogen bonding interactions and the dynamical aspects of solvation in ground and excited states. The computational protocol is successfully tested against experimentally measured spectra of water soluble fluorescent dyes, demonstrating its reliability and paving the way for cost-effective investigation of solvated systems' ES properties.
Article
Biochemistry & Molecular Biology
Yvonne Joho, Vanessa Vongsouthi, Matthew A. Spence, Jennifer Ton, Chloe Gomez, Li Lynn Tan, Joe A. Kaczmarski, Alessandro T. Caputo, Santana Royan, Colin J. Jackson, Albert Ardevol
Summary: Biocatalytic PET depolymerization is a sustainable and low-energy solution for PET recycling. This study applies ancestral protein reconstruction and protein repair one-stop shop to improve enzyme activity and stability, providing new insights into PETase activity evolution and the role of second-shell mutations around the active site.
Article
Biochemistry & Molecular Biology
Lisa M. Pietrek, Lukas S. Stelzl, Gerhard Hummer
Summary: Disordered proteins and nucleic acids are important in cellular function and disease. This review discusses recent advances in computationally exploring the dynamics of flexible biomolecules. While molecular dynamics simulation has improved, large-scale computing resources and validation are needed for simulating full-length disordered biopolymers. Hierarchical chain growth is a computationally efficient alternative that combines chain fragments into detailed biomolecular structures. Applications to neurodegeneration-linked proteins highlight the use of hierarchical chain growth, and connections to AI-based structural modeling are also discussed.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Soeren von Buelow, Mateusz Sikora, Florian E. C. Blanc, Roberto Covino, Gerhard Hummer
Summary: Since the start of the COVID-19 pandemic, the emergence of new variants has hindered the effectiveness of vaccines and made achieving herd immunity difficult. However, through molecular dynamics simulations of a SARS-CoV-2 spike protein model, researchers have found that the accessibility of antibodies to regions beyond the glycan shield can predict mutated positions in important variants like Omicron. This understanding of viral evolution and immune defense can help in predicting future mutation activity and escape from antibody-based immune responses.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Chemistry, Physical
Balazs Fabian, Sebastian Thallmair, Gerhard Hummer
Summary: Artificial temperature gradients were observed in MD simulations of phase-separating ternary lipid mixtures using the Martini 2 force field. This was traced back to insufficiently converged bond length constraints caused by default settings and time steps in the linear constraint solver (LINCS). By optimizing the constraint scaffold of cholesterol with equimomental arrangement of virtual sites, the bond constraint convergence can be accelerated while maintaining the original cholesterol force field and dynamics.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Jakob Tomas Bullerjahn, Soren von Bulow, Maziar Heidari, Jerome Henin, Gerhard Hummer
Summary: In molecular dynamics simulations, the size and shape of the simulation box may vary over time. Unbounded position displacements can occur when rescaling the box by the barostat for particle images far from the origin. This necessitates careful trajectory unwrapping and rewrapping methods for accurate calculations of translational diffusion coefficients.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Multidisciplinary Sciences
Miao Yu, Maziar Heidari, Sofya Mikhaleva, Piau Siong Tan, Sara Mingu, Hao Ruan, Christopher D. Reinkemeier, Agnieszka Obarska-Kosinska, Marc Siggel, Martin Beck, Gerhard Hummer, Edward A. Lemke
Summary: This study investigates the conformation of FG nucleoporin NUP98 inside the mammalian nuclear pore complex. The researchers used synthetic biology and time-resolved fluorescence microscopy to directly probe the structure in live cells and permeabilized cells. They found that the channel provides a "good solvent" environment, allowing the FG domain to adopt expanded conformations and control transport between the nucleus and cytoplasm.
Article
Multidisciplinary Sciences
Alexis Gonzalez, Adriana Covarrubias-Pinto, Ramachandra M. Bhaskara, Marius Glogger, Santosh K. Kuncha, Audrey Xavier, Eric Seemann, Mohit Misra, Marina E. Hoffmann, Bastian Braeuning, Ashwin Balakrishnan, Britta Qualmann, Volker Doetsch, Brenda A. Schulman, Michael M. Kessels, Christian A. Huebner, Mike Heilemann, Gerhard Hummer, Ivan Dikic
Summary: The endoplasmic reticulum (ER) can be remodeled through a selective autophagy pathway called ER-phagy. This study identified that ubiquitination of the ER-phagy receptor FAM134B promotes receptor clustering and binding to LC3B, stimulating ER-phagy. The results reveal the importance of ubiquitination in enhancing ER-phagy and controlling ER remodeling.
Article
Multidisciplinary Sciences
Hector Foronda, Yangxue Fu, Adriana Covarrubias-Pinto, Hartmut T. Bocker, Alexis Gonzalez, Eric Seemann, Patricia Franzka, Andrea Bock, Ramachandra M. M. Bhaskara, Lutz Liebmann, Marina E. E. Hoffmann, Istvan Katona, Nicole Koch, Joachim Weis, Ingo Kurth, Joseph G. G. Gleeson, Fulvio Reggiori, Gerhard Hummer, Michael M. M. Kessels, Britta Qualmann, Muriel Mari, Ivan Dikic, Christian A. A. Huebner
Summary: Membrane-shaping proteins containing reticulon homology domains are crucial for dynamic remodelling of the endoplasmic reticulum (ER). FAM134B is an example of such a protein, which mediates the degradation of ER sheets through a process called selective autophagy (ER-phagy) by binding to LC3 proteins. Mutations in FAM134B result in a neurodegenerative disorder in humans.
Correction
Multidisciplinary Sciences
Rong Zhu, Daniel Canena, Mateusz Sikora, Miriam Klausberger, Hannah Seferovic, Ahmad Reza Mehdipour, Lisa Hain, Elisabeth Laurent, Vanessa Monteil, Gerald Wirnsberger, Ralph Wieneke, Robert Tampe, Nikolaus F. Kienzl, Lukas Mach, Ali Mirazimi, Yoo Jin Oh, Josef M. Penninger, Gerhard Hummer, Peter Hinterdorfer
NATURE COMMUNICATIONS
(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
Biochemistry & Molecular Biology
Clara Lettl, Franziska Schindele, Ahmad Reza Mehdipour, Thomas Steiner, Diana Ring, Ruth Brack-Werner, Baerbel Stecher, Wolfgang Eisenreich, Ursula Bilitewski, Gerhard Hummer, Matthias Witschel, Wolfgang Fischer, Rainer Haas
Summary: Respiratory complex I plays an important role in cellular respiration of both eukaryotic cells and bacteria. The inhibition of complex I by mitochondrial complex I inhibitors can selectively kill Helicobacter pylori, a Gram-negative bacterial pathogen, while leaving other bacteria unaffected. The unique composition of the quinone-binding pocket in H. pylori complex I is responsible for this hypersensitivity, suggesting the potential of developing complex I inhibitors as narrow-spectrum antimicrobial agents against H. pylori.
CELL CHEMICAL BIOLOGY
(2023)
Article
Computer Science, Interdisciplinary Applications
Hendrik Jung, Roberto Covino, A. Arjun, Christian Leitold, Christoph Dellago, Peter G. Bolhuis, Gerhard Hummer
Summary: A machine learning algorithm accelerates the sampling of rare assembly events, uncovers their mechanisms, extrapolates them across chemical and thermodynamic space, and condenses the learned assembly mechanisms into a human-interpretable form.
NATURE COMPUTATIONAL SCIENCE
(2023)
Article
Chemistry, Physical
Hyuntae Kim, Balazs Fabian, Gerhard Hummer
Summary: This study highlights the issues of membrane deformation and pressure imbalance in molecular dynamics simulations when using default parameters. The problems are mainly caused by missed nonbonded interactions and unbalanced pressure tensor, which result from improper parameter settings.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Multidisciplinary Sciences
Amir Pandi, David Adam, Amir Zare, Van Tuan Trinh, Stefan L. Schaefer, Marie Burt, Bjorn Klabunde, Elizaveta Bobkova, Manish Kushwaha, Yeganeh Foroughijabbari, Peter Braun, Christoph Spahn, Christian Preusser, Elke Pogge von Strandmann, Helge B. Bode, Heiner von Buttlar, Wilhelm Bertrams, Anna Lena Jung, Frank Abendroth, Bernd Schmeck, Gerhard Hummer, Olalla Vazquez, Tobias J. Erb
Summary: This study demonstrates the potential of using deep learning and cell-free protein synthesis for the rapid and cost-effective production and testing of bioactive peptides. Through computational methods and experimental validation, the authors identified 30 functional peptides, including six with broad-spectrum activity against drug-resistant pathogens.
NATURE COMMUNICATIONS
(2023)
Article
Physics, Fluids & Plasmas
Jakob Tomas Bullerjahn, Balazs Fabian, Gerhard Hummer
Summary: This article presents an algorithm for generating random 4D rotation matrices, which has applications in robotics, computer vision, and rigid-body mechanics. The algorithm enables efficient sampling of the SO(4) group of 4D rotations.