Article
Chemistry, Physical
Johannes C. B. Dietschreit, Dennis J. J. Diestler, Andreas Hulm, Christian Ochsenfeld, Rafael Gomez-Bombarelli
Summary: In this study, we investigated the calculation of activation free energy in chemical reactions and found that the approximation of the free-energy profile can lead to large errors. By defining a new exact expression, we identified an unambiguous method for calculating the activation free energy. The results suggest that this approach has practical value in dealing with high-dimensional potential energy surfaces and selecting appropriate variables.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Hugo A. L. Filipe, Luis M. S. Loura, Maria Joao Moreno
Summary: Permeation through biomembranes is crucial for drugs to reach their targets, and the asymmetry of cell plasma membrane plays an important role in this process. This study investigates the interaction of a series of NBD-labeled amphiphiles with lipid bilayers of different compositions, including an asymmetric bilayer. The behavior of the amphiphiles during permeation, including their orientation, chain elongation, and H-bonding, is described. The permeability coefficients of the amphiphiles are also calculated, but quantitative agreement with experimental values could not be achieved.
Article
Biochemistry & Molecular Biology
Lijun Liang, Zhisen Zhang, Hongbo Wang, Jia-Wei Shen, Zhe Kong
Summary: Through more than 40 conductance events from microsecond molecular dynamics simulation, soft knock-on ion permeation mediated by water molecules in sodium channels was observed and confirmed. The change of average distance between four oxygen atoms in Glu177-Glu177 was found to play a crucial role in Na+ ion permeation. Exploration of the ionic conductance mechanism may guide the design of ion channel targeted drugs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Multidisciplinary
Benjamin W. J. Chen, Xinglong Zhang, Jia Zhang
Summary: Machine learning interatomic potentials, combined with active learning, enable fast and accurate modelling of solvents in catalytic reactions. This approach accelerates molecular dynamics simulations and accurately predicts key catalytic quantities, opening up possibilities for studying solvated catalysts.
Article
Chemistry, Physical
Nicola Piasentin, Guoping Lian, Qiong Cai
Summary: This study combines molecular dynamics (MD) simulation with COSMOmic method to predict the partition coefficients of active ingredients in cosmetics in the stratum corneum (SC) lipid bilayer. The results show that the MD/COSMOmic approach is a fast and valid method for predicting solute partitioning into SC lipids, which is important for the assessment of percutaneous absorption of skin care ingredients, dermatological drugs, and environmental pollutants.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Multidisciplinary Sciences
Lianghao Guo, Wenfei Bo, Kaicheng Wang, Shaomeng Wang, Yubin Gong
Summary: The study investigates the interaction of terahertz waves with ions in nerve cell channels and its potential effects. It finds that terahertz radiation can generate electromagnetic radiation in calcium channels and accelerate the transport of calcium ions. These findings provide a theoretical basis for the future application of terahertz waves in neurological treatments.
Article
Biochemical Research Methods
Kanji Miyabe, Shunta Inaba, Momoko Umeda
Summary: A moment analysis method was attempted to determine the permeability of lipid membranes. The method involved analyzing the first and second moments of elution peaks measured by liposome electrokinetic chromatography (LEKC). Using the example of coumarin elution peaks in a LEKC system, it was found that the moment analysis method could measure the lipid membrane permeability of coumarin across the lipid bilayer of liposomes. However, it was also noted that the method primarily provided information about adsorption/desorption kinetics at the lipid bilayer. Different moment equations were developed to determine the adsorption/desorption rate constants of coumarin from the LEKC data.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Biochemistry & Molecular Biology
Xiaolu Cheng, George Khelashvili, Harel Weinstein
Summary: The TMEM16 family of transmembrane proteins includes phospholipid scramblases (PLS) that can also function as ion channels. The mechanism of ion conduction in TMEM16 PLS is still unclear. Molecular dynamics simulations and free energy calculations were used to investigate the dynamic path of potassium ion translocation through an open groove state of nhTMEM16 and the effects of lipids on ion permeation. The results provide insight into the structural and energy parameters that enable ion permeation and the influence of lipids on the efficiency of ion permeation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Medicine, Research & Experimental
Eduardo R. Almeida, Priscila V. Z. Capriles Goliatt, Heilio F. Dos Santos, Fabien Picaud
Summary: This study reveals that encapsulating cisplatin into carbon nanohorns (CNH) is a promising nanoformulation for targeted drug delivery to tumor sites. Biased molecular dynamics simulations show a four-stage mechanism of transmembrane transport, with the insertion stage potentially enhancing the retention of cisplatin in tumor sites.
MOLECULAR PHARMACEUTICS
(2023)
Article
Engineering, Environmental
Andrew Z. Haddad, Akanksha K. Menon, Hyungmook Kang, Jeffrey J. Urban, Ravi S. Prasher, Robert Kostecki
Summary: The growing global demand for water has led to desalination technologies becoming the focus for producing freshwater from nontraditional sources. Among these, the use of thermally responsive ionic liquids in forward osmosis (FO) desalination, coupled with solar heat for regeneration, has shown great potential for energy-efficient and cost-effective desalination, as demonstrated in the successful treatment of produced water from oil wells in Southern California.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Chemistry, Physical
Gari Kasparyan, Jochen S. Hub
Summary: Electric fields play important roles in lipid membranes, especially in modeling transmembrane potentials. Two methods, external fields and charge imbalance, are compared in the context of membrane electroporation, showing that both methods are suitable for studying large-scale transitions of lipid membranes involving changes of membrane capacitance.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Massimo Mella, Andrea Tagliabue, Lorella Izzo
Summary: Through the study of model systems, it is found that surfaces with low charge densities and surface-tethered like-charged pendants can still attract each other. In addition to electrostatic interactions, the entropic component of the system plays a key role in defining the overall magnitude of the forces.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Aleksandra Drajkowska, Andrzej Molski
Summary: The amyloidogenicity and toxicity of amyloid peptides are influenced by their aggregation and interactions with lipid bilayers. The study using MARTINI model found that A/3(1-28) fragments form irreversible aggregates with strong peptide-peptide and peptide-lipid interactions. On the other hand, A/3(25-35) fragments form reversible aggregates with weaker interactions and accumulate at the membrane-solution interface irrespective of their initial spatial arrangement.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Lucia Morillas-Becerril, Sebastian Franco-Ulloa, Ilaria Fortunati, Roberto Marotta, Xiaohuan Sun, Giordano Zanoni, Marco De Vivo, Fabrizio Mancin
Summary: The study demonstrates that cationic gold nanoparticles functionalized with guanidinium groups can interact specifically and nondisruptively with phospholipid bilayer membranes, inducing membrane permeabilization by multivalent H-bonding interactions. These findings suggest potential applications for delivering nanoparticles and their cargos into cells and biological vesicles.
COMMUNICATIONS CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Sabahuddin Ahmad, Christoph Heinrich Strunk, Stephan N. Schott-Verdugo, Karl-Erich Jaeger, Filip Kovacic, Holger Gohlke
Summary: PlaF, a phospholipase A(1) from Pseudomonas aeruginosa, plays a role in altering membrane composition and fostering virulence. Molecular dynamics simulations provided insights into the access pathways of GPL substrates to the catalytic center, suggesting an acyl chain-first entry preference. The findings contribute to understanding the acyl chain-length specificity and potential development of PlaF inhibitors for antibiotic purposes.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Multidisciplinary
Sevde Puza, Stefanie Caesar, Chetan Poojari, Michael Jung, Ralf Seemann, Jochen S. Hub, Bianca Schrul, Jean-Baptiste Fleury
Summary: Lipid droplets (LDs) are organelles derived from the endoplasmic reticulum (ER) membrane and play a crucial role in lipid storage. The distribution of proteins between phospholipid bilayer and LD monolayer membranes is determined by the collective properties of protein-intrinsic and lipid-mediated features. In this study, researchers produced a freestanding phospholipid bilayer using microfluidics and observed the insertion of micrometer-sized LDs into the bilayer. They found that the LDs presented a lens shape and there was a diffusion barrier between the LD monolayer and the bilayer. This barrier may influence the partitioning of proteins between the ER membrane and LDs in living cells.
Article
Biochemistry & Molecular Biology
Alexander E. Yarawsky, Jesse B. Hopkins, Leonie Chatzimagas, Jochen S. Hub, Andrew B. Herr
Summary: This study investigates the structural characteristics of B-repeat mutant constructs of Aap from S. epidermidis using multiple techniques. The resulting models provide insights into the mechanisms of functional amyloid fibril formation by Aap, highlighting an important contributing factor to recurrent staphylococcal infections.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biophysics
Jeremy Lapierre, Jochen S. Hub
Summary: By using steered molecular dynamics simulations, we have revealed the continuous pathway of DNA opening in RNA polymerase II during transcription initiation. The interactions between DNA and protein play crucial roles in driving and stabilizing the process of DNA opening.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemical Research Methods
Jill Trewhella, Patrice Vachette, Jan Bierma, Clement Blanchet, Emre Brookes, Srinivas Chakravarthy, Leonie Chatzimagas, Thomas E. Cleveland, Nathan Cowieson, Ben Crossett, Anthony P. Duff, Daniel Franke, Frank Gabel, Richard E. Gillilan, Melissa Graewert, Alexander Grishaev, J. Mitchell Guss, Michal Hammel, Jesse Hopkins, Qingqui Huang, Jochen S. Hub, Greg L. Hura, Thomas C. Irving, Cy Michael Jeffries, Cheol Jeong, Nigel Kirby, Susan Krueger, Anne Martel, Tsutomu Matsui, Na Li, Javier Perezt, Lionel Porcar, Thierry Prange, Ivan Rajkovic, Mattia Rocco, Daniel J. Rosenberg, Timothy M. Ryan, Soenke Seifert, Hiroshi Sekiguchi, Dmitri Svergun, Susana Teixeira, Aurelien Thureaut, Thomas M. Weiss, Andrew E. Whitten, Kathleen Wood, Xiaobing Zuo
Summary: By collecting SAXS and SANS measurements, consensus scattering profiles for proteins were obtained, which were consistent with theoretical predictions. Optimization of sample purification methods and measurement conditions can improve the quality and precision of the data.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
David Roesel, Maksim Eremchev, Chetan S. Poojari, Jochen S. Hub, Sylvie Roke
Summary: A direct link between membrane potential fluctuations and divalent ion transport has been discovered, and it has been shown through molecular dynamics simulations and experimental results that pore formation induced by an ion-induced electrostatic field is a viable mechanism for unassisted ion transport.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Nele Merret Hollmann, Pravin Kumar Ankush Jagtap, Johanna-Barbara Linse, Philip Ullmann, Marco Payr, Brice Murciano, Bernd Simon, Jochen S. Hub, Janosch Hennig
Summary: RNA binding proteins (RBPs) use multiple RNA binding domains (RBDs) to increase target specificity and affinity. However, the complexity of target recognition by multiple RBDs is not well understood. This study demonstrates how multiple RBDs in the multidomain RBP Unr orchestrate target specificity. Structural analysis reveals the interaction surfaces between Unr and the poly(A)-binding protein (pAbp), providing insights into their cooperative role in cellular processes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Robert A. Becker, Jochen S. Hub
Summary: DEAH-box helicases are dynamic machines that use ATP hydrolysis to move along RNA strands. The presence of RNA makes the helicases more rigid, while the presence of ATP and ADP controls the stability of the RecA1-RecA2 interface. G-patch proteins have a subtle effect on the domain dynamics compared to RNA or ATP/ADP, but they impose a more structured conformational ensemble. These simulations provide insights into the conformational dynamics and regulation of DEAH-box helicases.
BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Carla F. Sousa, Robert A. Becker, Claus-Michael Lehr, Olga V. Kalinina, Jochen S. Hub
Summary: Molecular dynamics simulations were used to study solute permeation across biological membranes. The potential of mean force (PMF) for solute permeation was computed using enhanced sampling techniques such as umbrella sampling (US). However, obtaining converged PMFs for bulky drug-like permeants remains challenging and often requires long simulation times. Simulated tempering-enhanced umbrella sampling (STeUS) was employed to improve the convergence of PMF calculations and reduce the computational cost of routine high-throughput studies of drug permeability.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Gari Kasparyan, Jochen S. Hub
Summary: Electric fields play important roles in lipid membranes, especially in modeling transmembrane potentials. Two methods, external fields and charge imbalance, are compared in the context of membrane electroporation, showing that both methods are suitable for studying large-scale transitions of lipid membranes involving changes of membrane capacitance.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biology
Robert A. Becker, Jochen S. Hub
Summary: Helicases are motor enzymes that play important roles in maintaining genome stability and controlling recombination. Using molecular dynamics simulations, this study reveals the atomic-level conformational cycle of RNA translocation by the DEAH-box helicase Prp43. The findings highlight the complex atomic-scale transitions involved in the crawling movement of the helicase along RNA.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Jeremy Lapierre, Jochen S. Hub
Summary: The emergence of multidrug-resistant pathogens calls for the development of new antibiotics. Effective antibiotics against Gram-negative bacteria must be able to permeate the bacterial outer membrane via transmembrane porin proteins. However, obtaining accurate simulation results for antibiotic permeation across outer membrane porins has been challenging due to sampling problems.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Friederike Nolle, Leonhard J. Starke, Alessandra Griffo, Michael Lienemann, Karin Jacobs, Ralf Seemann, Jean-Baptiste Fleury, Jochen S. Hub, Hendrik Haehl
Summary: This study reports on the very low water permeability of pure protein membranes composed of a bilayer of amphiphilic protein hydrophobin HFBI. The low permeability of HFBI and lipid bilayers rely on different mechanisms. With their low permeability and high stability, HFBI membranes have important applications such as desalination membranes.
Article
Physics, Multidisciplinary
Leonie Chatzimagas, Jochen S. Hub
Summary: This study reveals the structural dynamics of shock waves produced after X-ray impact and their potential effects on biomolecular samples. Molecular dynamics simulations show that the shock waves travel supersonically along the liquid jet and decay with an attenuation length proportional to the jet diameter.
PHYSICAL REVIEW LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Michelangelo Marasco, John Kirkpatrick, Teresa Carlomagno, Jochen S. Hub, Massimiliano Anselmi
Summary: SHP2 is a critical protein involved in regulating cellular processes, and its mutations can lead to developmental disorders and cancer. The protein consists of multiple domains, including two SH2 domains and a catalytic PTP domain. The relative orientation and spacing between the SH2 domains play a crucial role in enzymatic activation. Previous studies have not provided a clear picture of the SH2 domain structure, but experiment-guided molecular simulations have revealed the structural flexibility of the tandem SH2 in solution, suggesting its importance in SHP2's functional activity.
Article
Chemistry, Multidisciplinary
Johanna-Barbara Linse, Jochen S. Hub
Summary: In this study, the authors use small-angle scattering data as a protein-specific probe to quantify the effect of protein charge and geometric shape on the hydration shell.
COMMUNICATIONS CHEMISTRY
(2023)