Article
Multidisciplinary Sciences
Jinzen Ikebe, Munenori Suzuki, Aya Komori, Kaito Kobayashi, Tomoshi Kameda
Summary: This paper presents a method called MSPER for enhancing the regioselectivity of substrate reaction sites by destabilizing binding poses for byproducts while maintaining those for target products. Applying MSPER to cytochrome P450 CYP102A1 (BM3) and two substrates resulted in successfully enhancing the regioselectivity for four target products with different reaction sites.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ai Shinobu, Suyong Re, Yuji Sugita
Summary: Molecular dynamics (MD) simulations are used to study biological processes, but conventional methods are not effective for slow dynamics. Researchers applied a two-dimensional replica-exchange MD method and optimized the simulation protocols to achieve accurate results and good random sampling.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Aayush Gupta, Souvik Dey, Alan Hicks, Huan-Xiang Zhou
Summary: This study developed generative autoencoders that can learn from short molecular dynamics simulations and generate full conformational ensembles of intrinsically disordered proteins.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ameya Harmalkar, Jeffrey J. Gray
Summary: Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility can hinder accurate predictions. Recent advances include enhanced sampling techniques and internal coordinate formulations to address the issue of protein backbone flexibility.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paolo Calligari, Valerio Santucci, Lorenzo Stella, Gianfranco Bocchinfuso
Summary: SHP2 is a critical player in signaling pathways, with activation involving rearrangement of domains and binding to proteins containing phosphotyrosines. Studies show the crystallographic conformation is unstable in solution, with multiple interdomain arrangements present, and activation is coupled to changes in the N-SH2 binding site.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Immunology
Martin Kulke, Felix Nagel, Lukas Schulig, Norman Geist, Marcel Gabor, Julia Mayerle, Markus M. Lerch, Andreas Link, Mihaela Delcea
Summary: The study identified two main binding states of the inhibitor to the complex, explicitly relating the influence of the mutation site to conformational changes in the active site of trypsin. Based on the results, a hypothesis was formulated that explains the development of chronic pancreatitis through accelerated digestion of the mutant by trypsin.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Rajeswari Appadurai, Jayashree Nagesh, Anand Srivastava
Summary: The study introduces a parallel-tempering method that utilizes accelerated water dynamics for efficient and accurate conformational sampling across a wide variety of proteins, demonstrating successful application to large metamorphic proteins and highly disordered proteins with good fit to experimental data.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Sridip Parui, James C. Robertson, Sandeep Somani, Gary Tresadern, Cong Liu, Ken A. Dill
Summary: The study developed the MELD-Bracket method for efficient affinity ranking of structurally diverse small molecule ligands in structure-based drug discovery. The method was tested on multiple protein systems and showed a balanced accuracy and computational efficiency in ranking different ligands.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Piotr Chyzy, Marta Kulik, Suyong Re, Yuji Sugita, Joanna Trylska
Summary: Short, structured fragments of non-coding mRNA may act as molecular switches upon binding specific ligands, regulating the translation of proteins encoded downstream this mRNA sequence. The study reveals that nucleobase mutations in the riboswitch can significantly affect the affinity and efficiency of ligand regulation, with specific mutations altering the binding site position of neomycin and increasing its flexibility.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Iga Biskupek, Cezary Czaplewski, Justyna Sawicka, Emilia Ilowska, Maria Dzierzynska, Sylwia Rodziewicz-Motowidlo, Adam Liwo
Summary: The UNited RESidue (UNRES) model was used to study the aggregation behavior of 20 peptides with different lengths. The majority of peptides showed inter-strand beta-sheet formation, except for glutamine- and asparagine-rich peptides, which require modification of the UNRES model.
Article
Chemistry, Physical
Curtis Goolsby, James Losey, Ashkan Fakharzadeh, Yuchen Xu, Marie-Christine Duker, Mila Getmansky Sherman, David S. Matteson, Mahmoud Moradi
Summary: Markov State Models (MSM) and related techniques are widely used in molecular dynamics (MD) simulations to extract structural, thermodynamic, and kinetic information on proteins. This work proposes an alternative approach using the rate/generator matrix instead of the transition matrix for estimating thermodynamic and kinetic quantities, particularly in diffusive processes. The key contribution of this work is the introduction of a novel method to address the embeddability problem and the utilization of existing algorithms. The algorithms are tested on a one-dimensional toy model to demonstrate their effectiveness and robustness.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Article
Chemistry, Physical
Vojtech Mlynsky, Petra Kuhrova, Petr Stadlbauer, Miroslav Krepl, Michal Otyepka, Pavel Banas, Jiri Sponer
Summary: Molecular dynamics simulations are commonly used to study RNA molecules. By adjusting the nonbonded parameters, the widely used AMBER OL3 ff in RNA simulations can be improved. The modified simulations show better agreement with experimental results.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Ali A. Alizadehmojarad, Sergei M. Bachilo, R. Bruce Weisman
Summary: Aqueous suspensions of single-wall carbon nanotubes coated by ssDNA were analyzed to determine the absolute average concentrations of both components and the absorptivity values of the nanotubes. The results provide a method to measure the absolute concentrations of similar SWCNT samples in aqueous SDS using simple spectrophotometry. The study also quantifies the mass ratio of ssDNA to SWCNT and compares experimental results with molecular dynamics simulations.
Article
Chemistry, Physical
Christopher C. Walker, Garrett A. Meek, Theodore L. Fobe, Michael R. Shirts
Summary: In this paper, a Python-based simulation framework, cg_openmm, is introduced for modeling coarse-grained hetero-oligomers and screening them for structural and thermodynamic characteristics. The framework includes tools for building topology, setting up simulations, and analyzing thermodynamic and structural properties. The capabilities of cg_openmm are demonstrated on a simple coarse-grained model, showing the formation of stable helices through cooperative folding transitions and the tunability of helix geometries and stabilities by manipulating force-field parameters.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Haochuan Chen, Haohao Fu, Christophe Chipot, Xueguang Shao, Wensheng Cai
Summary: GaWTM-eABF is a hybrid algorithm that introduces the GaMD softened potential into WTM-eABF, effectively overcoming free-energy barriers in orthogonal space and accurately recovering unbiased free-energy landscape. Numerical tests demonstrate that GaWTM-eABF reduces uncertainty in PMF calculation and converges faster than WTM-eABF.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
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.
Article
Biochemistry & Molecular Biology
Di Wu, Ahmad R. R. Mehdipour, Franziska Finke, Hojjat G. G. Goojani, Roan R. R. Groh, Tamara N. N. Grund, Thomas M. B. Reichhart, Rita Zimmermann, Sonja Welsch, Dirk Bald, Mark Shepherd, Gerhard Hummer, Schara Safarian
Summary: CydDC is a protein transporter responsible for the transport of heme, a redox-active cofactor, from the cytoplasm to the respiratory chain complexes, playing a crucial role in cellular respiration. Through the integrated use of cellular, biochemical, structural and computational methods, the structure and function of CydDC, as well as its mechanism in the functional maturation of cytochrome bd, have been revealed.
NATURE CHEMICAL BIOLOGY
(2023)
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
Wout Oosterheert, Florian E. C. Blanc, Ankit Roy, Alexander Belyy, Micaela Boiero Sanders, Oliver Hofnagel, Gerhard Hummer, Peter Bieling, Stefan Raunser
Summary: This study reveals the mechanism of inorganic phosphate (Pi) release from actin through a 'molecular backdoor' by combining cryo-EM, molecular-dynamics simulations, and in vitro reconstitution. The backdoor opens transiently through amino acid rearrangements, explaining the rapid release of Pi from the filament end and slow release from internal subunits. The study also finds that a disease-linked actin variant distorts the backdoor arrangement, resulting in accelerated Pi release.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(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)