Journal Description
Biophysica
Biophysica
is an international, peer-reviewed, open access journal on applying the methods of physics, chemistry, and math to study biological systems, published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, EBSCO, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.9 days after submission; acceptance to publication is undertaken in 4.9 days (median values for papers published in this journal in the first half of 2023).
- Recognition of reviewers: APC discount vouchers, optional signed peer review and reviewer names are published annually in the journal.
- Biophysica is a companion journal of IJMS.
Latest Articles
Screening and Analysis of Potential Inhibitors of SHMT2
Biophysica 2023, 3(4), 651-667; https://doi.org/10.3390/biophysica3040044 (registering DOI) - 03 Dec 2023
Abstract
Serine hydroxymethyltransferase 2 (SHMT2) has garnered significant attention as a critical catalytic regulator of the serine/glycine pathway in the one-carbon metabolism of cancer cells. Despite its potential as an anti-cancer target, only a limited number of inhibitors have been identified so far. In
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Serine hydroxymethyltransferase 2 (SHMT2) has garnered significant attention as a critical catalytic regulator of the serine/glycine pathway in the one-carbon metabolism of cancer cells. Despite its potential as an anti-cancer target, only a limited number of inhibitors have been identified so far. In this study, we employed seven different scoring functions and skeleton clustering to screen the ChemDiv database for 38 compounds, 20 of which originate from the same skeleton structure. The most significant residues from SHMT2 and chemical groups from the inhibitors were identified using ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy), and the binding energy of each residue was quantitatively determined, revealing the essential features of the protein–inhibitor interaction. The two most important contributing residues are TYR105 and TYR106 of the B chain followed by LEU166 and ARG425 of the A chain. The findings will be greatly helpful in developing a thorough comprehension of the binding mechanisms involved in drug–SHMT2 interactions and offer valuable direction for designing more potent inhibitors.
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(This article belongs to the Special Issue Molecular Structure and Simulation in Biological System 2.0)
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Microgravity as an Anti-Metastatic Agent in an In Vitro Glioma Model
by
, , , , and
Biophysica 2023, 3(4), 636-650; https://doi.org/10.3390/biophysica3040043 - 25 Nov 2023
Abstract
Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported
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Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported by cytoskeletal dynamics and surface proteins that allow glioblastoma cells to avoid stable connections with the tissue environment and other cells. Glioblastoma cell line C6 was exposed to a microgravity environment for 24, 48, and 72 h by 3D-RPM, a laboratory instrument recognized to reproduce the effect of microgravity in cell cultures. The immunofluorescence for GFAP, vinculin, and Connexin-43 was investigated as signals related to cytoskeleton dynamics. The polymerization of GFAP and the expression of focal contact structured by vinculin were found to be altered, especially after 48 and 72 h of microgravity. Connexin-43, involved in several intracellular pathways that critically promote cell motility and invasion of glioma cells, was found to be largely reduced following microgravity exposure. In conclusion, microgravity, by reducing the expression of Connexin-43, alters the architecture of specific cytoskeletal elements such as GFAP and increases the focal contact, which can induce a reduction in glioma cell mobility, thereby inhibiting their aggressive metastatic behavior.
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(This article belongs to the Special Issue State-of-the-Art Biophysics in Italy)
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Investigating the Insertion Mechanism of Cell-Penetrating Peptide Penetratin into Cell Membranes: Implications for Targeted Drug Delivery
Biophysica 2023, 3(4), 620-635; https://doi.org/10.3390/biophysica3040042 - 11 Nov 2023
Abstract
The cell-penetrating peptide (CPP) penetratin (PEN) has garnered attention for its potential to enter tumor cells. However, its translocation mechanism and lack of selectivity remain debated. This study investigated PEN’s insertion into healthy cells (H-) and cancer cells (C-) using micromolar concentrations and
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The cell-penetrating peptide (CPP) penetratin (PEN) has garnered attention for its potential to enter tumor cells. However, its translocation mechanism and lack of selectivity remain debated. This study investigated PEN’s insertion into healthy cells (H-) and cancer cells (C-) using micromolar concentrations and various techniques. Raman spectroscopy was used to determine PEN’s location in the lipid bilayer at different lipid-to-peptide ratios. Dynamic light scattering (DLS) and zeta potential analysis were used to measure the lipid–PEN complex’s size and charge. The results showed helical PEN particles directly inserted into C- membranes at a ratio of 110, while aggregated particles stayed on H- surfaces. Raman spectroscopy and scanning electron microscopy confirmed PEN insertion in C- membranes. Zeta potential studies revealed highly negative charges for PEN–C- complexes and neutral charges for PEN–H- complexes at pH 6.8. C- integrity remained unchanged at a ratio of 110. Specific lipid-to-peptide ratios with dipalmitoylphosphatidylserine (DPPS) were crucial for direct insertion. These results provide valuable insights into CPP efficacy for targeted drug delivery in cancer cells, considering membrane composition and lipid-to-peptide ratios.
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(This article belongs to the Special Issue Biomedical Optics 2.0)
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Physical Virology in Spain
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, , , , , and
Biophysica 2023, 3(4), 598-619; https://doi.org/10.3390/biophysica3040041 - 31 Oct 2023
Abstract
Virus particles consist of a protein coat that protects their genetic material and delivers it to the host cell for self-replication. Understanding the interplay between virus structure and function is a requirement for understanding critical processes in the infectious cycle such as entry,
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Virus particles consist of a protein coat that protects their genetic material and delivers it to the host cell for self-replication. Understanding the interplay between virus structure and function is a requirement for understanding critical processes in the infectious cycle such as entry, uncoating, genome metabolism, capsid assembly, maturation, and propagation. Together with well-established techniques in cell and molecular biology, physical virology has emerged as a rapidly developing field, providing detailed, novel information on the basic principles of virus assembly, disassembly, and dynamics. The Spanish research community contains a good number of groups that apply their knowledge on biology, physics, or chemistry to the study of viruses. Some of these groups got together in 2010 under the umbrella of the Spanish Interdisciplinary Network on Virus Biophysics (BioFiViNet). Thirteen years later, the network remains a fertile ground for interdisciplinary collaborations geared to reveal new aspects on the physical properties of virus particles, their role in regulating the infectious cycle, and their exploitation for the development of virus-based nanotechnology tools. Here, we highlight some achievements of Spanish groups in the field of physical virology.
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(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain 2.0)
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Elucidating the Influence of Lipid Composition on Bilayer Perturbations Induced by the N-Terminal Region of the Huntingtin Protein
Biophysica 2023, 3(4), 582-597; https://doi.org/10.3390/biophysica3040040 - 28 Oct 2023
Abstract
Understanding the membrane interactions of the N-terminal 17 residues of the huntingtin protein (HttN) is essential for unraveling its role in cellular processes and its impact on huntingtin misfolding. In this study, we used atomic force microscopy (AFM) to examine the effects of
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Understanding the membrane interactions of the N-terminal 17 residues of the huntingtin protein (HttN) is essential for unraveling its role in cellular processes and its impact on huntingtin misfolding. In this study, we used atomic force microscopy (AFM) to examine the effects of lipid specificity in mediating bilayer perturbations induced by HttN. Across various lipid environments, the peptide consistently induced bilayer disruptions in the form of holes. Notably, our results unveiled that cholesterol enhanced bilayer perturbation induced by HttN, while phosphatidylethanolamine (PE) lipids suppressed hole formation. Furthermore, anionic phosphatidylglycerol (PG) and cardiolipin lipids, along with cholesterol at high concentrations, promoted the formation of double-bilayer patches. This unique structure suggests that the synergy among HttN, anionic lipids, and cholesterol can enhance bilayer fusion, potentially by facilitating lipid intermixing between adjacent bilayers. Additionally, our AFM-based force spectroscopy revealed that HttN enhanced the mechanical stability of lipid bilayers, as evidenced by an elevated bilayer puncture force. These findings illuminate the complex interplay between HttN and lipid membranes and provide useful insights into the role of lipid composition in modulating membrane interactions with the huntingtin protein.
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(This article belongs to the Collection Feature Papers in Biophysics)
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Fractal Dimension Analyses to Detect Alzheimer’s and Parkinson’s Diseases Using Their Thin Brain Tissue Samples via Transmission Optical Microscopy
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, , , , and
Biophysica 2023, 3(4), 569-581; https://doi.org/10.3390/biophysica3040039 - 26 Oct 2023
Abstract
Biological tissues in nature are fractal due to their self-similarity and porosity properties. These properties change with the progress of some diseases, including brain tissue in leading neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Thus, there is an unmet
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Biological tissues in nature are fractal due to their self-similarity and porosity properties. These properties change with the progress of some diseases, including brain tissue in leading neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Thus, there is an unmet clinical need to develop a tool for accurate and early diagnosis of AD and PD conditions. Although the whole brain tissues in AD and PD have been extensively studied, their local structural alterations at the nano-to-submicron levels have not been explored. In this paper, we measure the local structural alterations in different brain regions of AD and PD patients by measuring their change in fractal dimensions via optical microscopy. Our results show an increase in the fractal dimension value of ~5–10% in the affected regions of the brain tissues relative to their respective controls. For AD cases, the structural alteration is attributed to the aberrant deposition of amyloid beta protein and neurofibrillary tangles in the brain, and for PD, the gradual loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the brain. The work will enhance the further understanding of alterations in the brain structures in AD and PD and its detection.
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(This article belongs to the Special Issue Biomedical Optics 2.0)
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Inactivating Host Bacteria for Characterization and Use of Phages
Biophysica 2023, 3(4), 558-568; https://doi.org/10.3390/biophysica3040038 - 27 Sep 2023
Abstract
Phage characterization for research and therapy can involve newly isolated phages propagated in pathogenic bacteria. If so, characterization requires safety-managing the bacteria. In the current study, we adapt a common and inexpensive reagent, PrimeStore (Longhorn Vaccines and Diagnostics, San Antonio, TX, USA), to
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Phage characterization for research and therapy can involve newly isolated phages propagated in pathogenic bacteria. If so, characterization requires safety-managing the bacteria. In the current study, we adapt a common and inexpensive reagent, PrimeStore (Longhorn Vaccines and Diagnostics, San Antonio, TX, USA), to safety-manage bacteria in 20 min by selectively inactivating the bacteria. No bacterial survivors are observed among >109 bacteria per ml for a representative of both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Bacillus thuringiensis). This procedure causes no detected inactivation of podophage T3, myophage T4 and siphophage 0105phi7-2. Margins of safety for PrimeStore concentration exist for bacterial inactivation and phage non-inactivation. Thus, general applicability is expected. Subsequent dialysis is used to block long-term effects on phages. Nonetheless, comparable tests should be performed for each pathogenic bacterial strain/phage. Electron microscopy of thin sections reveals inactivation-altered bacterial cytoplasm and a non-disintegrated bacterial envelope (ghosts). Ghosting of E. coli includes re-arrangement of the cytoplasm and the release of endotoxin. The activity of the released endotoxin is >99% reduced after subsequent dialysis, which also removes PrimeStore components. Ghosting of B. thuringiensis includes apparent phase separation within the cytoplasm. The primary application envisaged is biophysical and other screening of phages for therapy of infectious disease.
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(This article belongs to the Special Issue Biomedical Optics)
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A Dynamic Representation of mRNA Nucleotides Clarifies the Conundrum of Codon Redundancy
Biophysica 2023, 3(3), 548-557; https://doi.org/10.3390/biophysica3030037 - 11 Sep 2023
Abstract
The deciphering of the genetic code takes place through the reading of the nitrogenous bases, which are four in number. In most cases, the bases are taken three by three, thus generating 64 possible combinations with repetition. Each combination (codon) allows for the
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The deciphering of the genetic code takes place through the reading of the nitrogenous bases, which are four in number. In most cases, the bases are taken three by three, thus generating 64 possible combinations with repetition. Each combination (codon) allows for the synthesis of a specific amino acid. Since the latter are only 21 in number, the codon-amino acid conversion table shows a strong redundancy. Countless efforts have been made to understand the true encryption mechanism. Here, we want to add our version, which consists of associating a periodic sound based on three notes to each codon. RNA now becomes a dynamic object and not just a list of static instructions. In addition to a different interpretation of the genetic code, there is also a considerable reduction in redundancy, given that the number of periodic sounds that can be produced with three notes drops to 20 (with the addition of four pure frequencies). Finally, we discuss the possibility of how these sounds can be generated and travel inside the double helix, and possibly emitted as biophotons.
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(This article belongs to the Special Issue Biomedical Optics)
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Detecting Molecular Folding from Noise Measurements
by
and
Biophysica 2023, 3(3), 539-547; https://doi.org/10.3390/biophysica3030036 - 05 Sep 2023
Abstract
Detecting conformational transitions in molecular systems is key to understanding biological processes. Here, we investigate the force variance in single-molecule pulling experiments as an indicator of molecular folding transitions. We consider cases where Brownian force fluctuations are large, masking the force rips and
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Detecting conformational transitions in molecular systems is key to understanding biological processes. Here, we investigate the force variance in single-molecule pulling experiments as an indicator of molecular folding transitions. We consider cases where Brownian force fluctuations are large, masking the force rips and jumps characteristics of conformational transitions. We compare unfolding and folding data for DNA hairpin systems of loop sizes 4, 8, and 20 and the 110-amino acid protein barnase, finding conditions that facilitate the detection of folding events at low forces where the signal-to-noise ratio is low. In particular, we discuss the role of temperature as a useful parameter to improve the detection of folding transitions in entropically driven processes where folding forces are temperature independent. The force variance approach might be extended to detect the elusive intermediate states in RNA and protein folding.
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(This article belongs to the Special Issue State-of-the-Art Biophysics in Spain 2.0)
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Probing Biochemical Differences in Lipid Components of Human Cells by Means of ATR-FTIR Spectroscopy
Biophysica 2023, 3(3), 524-538; https://doi.org/10.3390/biophysica3030035 - 01 Sep 2023
Abstract
Infrared spectroscopy has emerged as a promising technique for studying the composition of biological samples like lipids that play important roles in cellular functions and are involved in various diseases. For this reason, lipids are a target of interest in many biomedical studies.
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Infrared spectroscopy has emerged as a promising technique for studying the composition of biological samples like lipids that play important roles in cellular functions and are involved in various diseases. For this reason, lipids are a target of interest in many biomedical studies. The objective of the present study is to utilize Fourier-Transform Infrared (FT-IR) spectroscopy to examine the main lipid components of human cells (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, C18 ceramide, sphingosine-1-phosphate, ceramide-1-phosphate, sphingomyelin, cholesterol, and triolein). FT-IR analysis on the previously mentioned lipid samples was performed in Attenuated Total Reflection (ATR) mode. The obtained spectra clearly evidence the contributions of the different functional groups that are present in the examined samples. Detailed assignments of spectral features were carried out in agreement with the literature. Similarities and differences among the different types of commercial lipid samples are evidenced and discussed, with particular attention to phospholipid and sphingolipid components. A quantitative analysis of phosphatidylinositol and sphingomyelin spectra using a ratiometric approach is reported. Moreover, a reconstruction procedure of FT-IR spectra of complex lipids useful for chemometrics applications is described. These representative examples of the potential use of the results of the present study can certainly contribute to a larger use of FT-IR spectroscopy in lipidomics.
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(This article belongs to the Special Issue Biomedical Optics)
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Experimental Determination of the Stability of the «Flamena» Gel Pharmacological Structure under the Influence of Low-Intensity Laser Radiation
Biophysica 2023, 3(3), 513-523; https://doi.org/10.3390/biophysica3030034 - 30 Aug 2023
Abstract
In modern dentistry, the problem of the prevention and treatment of peri-implantitis is relevant. Proposed methods of treating patients with peri-implantitis do not stop the pathological process with the possibility of achieving long-term remission. Liposomal complexes with dihydroquercetin make it possible to influence
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In modern dentistry, the problem of the prevention and treatment of peri-implantitis is relevant. Proposed methods of treating patients with peri-implantitis do not stop the pathological process with the possibility of achieving long-term remission. Liposomal complexes with dihydroquercetin make it possible to influence the pathogenetic links of the inflammatory process in periodontal tissues with the prospect of normalizing blood circulation and regeneration processes in the affected area. It has been established that the complex simultaneous effect of low-intensity laser radiation and a pharmaceutical (laserophoresis) provides the possibility of more significant penetration of the drug components into periodontal tissues. The study of the laserophoresis of the liposomal complex with dihydroquercetin in the treatment of patients with peri-implantitis is relevant. However, in the modern literature, there is a lack of studies on the effect of low-intensity laser radiation on the pharmaceutical structure of drugs based on the above-mentioned basis.
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(This article belongs to the Special Issue Biomedical Optics)
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Beta-Caryophyllene Induces Significant Changes in the Lipid Bilayer at Room and Physiological Temperatures: ATR-FTIR Spectroscopy Studies
Biophysica 2023, 3(3), 501-512; https://doi.org/10.3390/biophysica3030033 - 30 Aug 2023
Abstract
Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene with high biological activity. Potentially, it can be used in the treatment of a wide range of neurological diseases. However, to date, there are practically no data on the interaction of BCP with biological membranes. In
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Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene with high biological activity. Potentially, it can be used in the treatment of a wide range of neurological diseases. However, to date, there are practically no data on the interaction of BCP with biological membranes. In the present work, we studied for the first time the interaction of BCP with model membranes—liposomes based on egg yolk phosphatidylcholine (Egg PC) with a variable cholesterol content (from 0 to 25 w.%). Using ATR-FTIR spectroscopy, we have shown that the membrane rigidity and cholesterol content dramatically affect the nature of the interaction of BCP with the bilayer both at room temperature and at physiological temperatures. The incorporation of BCP into the thickness of the bilayer leads to changes in the subpolar region of the bilayer, and at a high cholesterol content, it can provoke the formation of defects in the membrane.
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(This article belongs to the Special Issue Biomedical Optics)
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Exploring Quercetin Hydrate’s Potential as an Antiviral Treatment for Oropouche Virus
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, , , , , , , , , and
Biophysica 2023, 3(3), 485-500; https://doi.org/10.3390/biophysica3030032 - 12 Aug 2023
Abstract
The Oropouche virus is an orthobunyavirus responsible for causing Oropouche fever, a disease that primarily affects thousands of people in South and Central America. Currently, no specific antiviral treatments or vaccines are available against this virus, highlighting the urgent need for safe, affordable,
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The Oropouche virus is an orthobunyavirus responsible for causing Oropouche fever, a disease that primarily affects thousands of people in South and Central America. Currently, no specific antiviral treatments or vaccines are available against this virus, highlighting the urgent need for safe, affordable, and effective therapies. Natural products serve as an important source of bioactive compounds, and there is growing interest in identifying natural bioactive molecules that could be used for treating viral diseases. Quercetin hydrate is a compound classified as a flavonoid, which has garnered scientific attention due to its potential health benefits and its presence in various plant-based foods. In this study, we aim to evaluate the in vitro antiviral activity of quercetin hydrate against the Oropouche virus (OROV). Furthermore, we intend to explore its mode of action through in silico approaches. The cytotoxicity and antiviral activity of the compound were assessed using Vero cells. In addition, in silico studies were also performed through molecular docking, molecular dynamics simulations, Molecular Mechanics Poisson–Boltzmann surface area (MM/PBSA), and quantum-mechanical analysis in order to evaluate the interaction with the Gc protein of OROV. The assay revealed that the compound was highly active against the virus, inhibiting OROV with an EC50 value of 53.5 ± 26.5 µM under post-infection treatment conditions. The present study demonstrates that the compound is a promising antiviral agent; however, the mechanisms of action proposed in this study need to be experimentally verified by future assays.
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(This article belongs to the Special Issue Molecular Structure and Simulation in Biological System 2.0)
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The Dynamic Behavior of a Single Semiflexible Ring Chain in a Linear Polymer Matrix
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and
Biophysica 2023, 3(3), 476-484; https://doi.org/10.3390/biophysica3030031 - 26 Jul 2023
Abstract
We studied the dynamic behavior of a single semiflexible ring in linear chain matrix based on a coarse-grained model using the molecular dynamics simulation approach. We found that that ring chains’ hollow centers are frequently filled with linear chains. However, as the rigidity
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We studied the dynamic behavior of a single semiflexible ring in linear chain matrix based on a coarse-grained model using the molecular dynamics simulation approach. We found that that ring chains’ hollow centers are frequently filled with linear chains. However, as the rigidity of the linear chains increases, the linear chains arranged parallel to each other and the ring chain are temporary caged. As a result, the swing movement in the normal direction of the ring is significantly limited, and the relaxation time in the normal direction increases significantly. Our findings can help to understand the physical mechanism of the movement of the ring chain in ring–linear polymer blends at the microscopic level.
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(This article belongs to the Special Issue Molecular Structure and Simulation in Biological System)
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Exploring the Dynamics of Holo-Shikimate Kinase through Molecular Mechanics
Biophysica 2023, 3(3), 463-475; https://doi.org/10.3390/biophysica3030030 - 21 Jul 2023
Abstract
Understanding the connection between local and global dynamics can provide valuable insights into enzymatic function and may contribute to the development of novel strategies for enzyme modulation. In this work, we investigated the dynamics at both the global and local (active site) levels
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Understanding the connection between local and global dynamics can provide valuable insights into enzymatic function and may contribute to the development of novel strategies for enzyme modulation. In this work, we investigated the dynamics at both the global and local (active site) levels of Shikimate Kinase (SK) through microsecond time-scale molecular dynamics (MD) simulations of the holoenzyme in the product state. Our focus was on the wild-type (WT) enzyme and two mutants (R116A and R116K) which are known for their reduced catalytic activity. Through exploring the dynamics of these variants, we gained insights into the role of residue R116 and its contribution to overall SK dynamics. We argue that the connection between local and global dynamics can be attributed to local frustration near the mutated residue which perturbs the global protein dynamics.
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(This article belongs to the Collection Feature Papers in Biophysics)
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A Structure-Guided Designed Small Molecule Is an Anticancer Agent and Inhibits the Apoptosis-Related MCL-1 Protein
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, , , , , , , , , , and
Biophysica 2023, 3(3), 446-462; https://doi.org/10.3390/biophysica3030029 - 07 Jul 2023
Abstract
Cancer resistance to chemotherapy and radiation therapies presents significant challenges, necessitating the exploration of alternative approaches. Targeting specific proteins at the molecular level, particularly their active sites, holds promise in addressing this issue. We investigated the potential of 4′-methoxy-2-nitrochalcone (MNC) as an MCL-1
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Cancer resistance to chemotherapy and radiation therapies presents significant challenges, necessitating the exploration of alternative approaches. Targeting specific proteins at the molecular level, particularly their active sites, holds promise in addressing this issue. We investigated the potential of 4′-methoxy-2-nitrochalcone (MNC) as an MCL-1 inhibitor, examining its chemical and structural characteristics to elucidate its biological activity and guide the selection of potential candidates. We conducted a docking study, followed by synthesis, structural characterization, theoretical calculations, and in vitro experiments to comprehensively evaluate MNC. The docking results revealed MNC’s excellent binding within the active site of MCL-1. At 50 µM, MNC demonstrated 99% inhibition of HCT116 cell proliferation, with an IC50 value of 15.18 µM after 24 h. Treatment with MNC at 30.36 and 15.18 µM resulted in reduced cell density. Notably, MNC exhibited marked cytotoxicity at concentrations of 15.58 µM and 7.79 µM, inducing high frequencies of plasma membrane rupture and apoptosis, respectively. Our findings highlight the significant biological potential of MNC as an MCL-1 inhibitor. Furthermore, we propose exploring chalcones with hydrogen bond acceptor substituents as promising candidates for studying inhibitors targeting this protein. In conclusion, our study addresses the challenge of cancer resistance by investigating MNC as an MCL-1 inhibitor. Through detailed characterization and experimental validation, we establish the efficacof MNC in inhibiting cell proliferation and inducing cytotoxic effects. These results underscore the potential of MNC as a valuable therapeutic agent and suggest the use of chalcones with hydrogen bond acceptor substituents as a basis for developing novel MCL-1 inhibitors.
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(This article belongs to the Collection Feature Papers in Biophysics)
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Screening for Bioactive Metabolites in Leaves, Branches, and Roots of Mansoa hirsuta: Phytochemical, Toxicological and Antioxidant Aspects
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, , , , , , , , , , and
Biophysica 2023, 3(3), 425-445; https://doi.org/10.3390/biophysica3030028 - 28 Jun 2023
Abstract
In this study, secondary metabolites, toxicology and antioxidant properties of chloroform fractions from leaves (FCFMh), branches (FCGMh), and roots (FCRMh) of Mansoa hirsuta were investigated. The phytochemical screening detected flavonoids, especially chalcones. Through Liquid chromatography with mass spectrometry—LC–MS analysis, the flavonoids (isoorientin-2″-O
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In this study, secondary metabolites, toxicology and antioxidant properties of chloroform fractions from leaves (FCFMh), branches (FCGMh), and roots (FCRMh) of Mansoa hirsuta were investigated. The phytochemical screening detected flavonoids, especially chalcones. Through Liquid chromatography with mass spectrometry—LC–MS analysis, the flavonoids (isoorientin-2″-O-arabinoside), triterpenes (oleanolic acid and ursolic acid) and ceramide (phytosphingosine) were identified. From the Artemia salina assay, the fraction FCGMh was the most toxic (LC50 = 64.21 µg·mL−1), followed by FCRMh (LC50 = 87.61 µg·mL−1) and FCFMh (LC50 = 421.9 µg·mL−1). Concerning the cytotoxic potential, the root fraction (IC50 16.48 μg mL−1) displayed the highest cytotoxicity against the breast cancer cell line (4T1), followed by leaves (IC50 33.13 μg mL−1) and branches (IC50 of 47.13 μg mL−1). In conclusion, all the fractions of M. hirsuta showed cytotoxicity at the highest concentrations; however, remarkable biological properties were found for the root fractions. Computational analysis was performed using a molecular docking and pharmacophore approach to understand the antioxidant activity of its major metabolites.
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(This article belongs to the Special Issue Molecular Structure and Simulation in Biological System)
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Adsorption of Heparin-Binding Fragments of Fibronectin onto Hydrophobic Surfaces
Biophysica 2023, 3(3), 409-424; https://doi.org/10.3390/biophysica3030027 - 23 Jun 2023
Abstract
Fibronectin is a multi-domain, extracellular matrix protein that plays a number of biological roles. As the adsorption of fibronectin onto the surface of implanted devices can lead to an inflammatory response or bacterial colonisation, understanding the interaction of fibronectin with material surfaces is
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Fibronectin is a multi-domain, extracellular matrix protein that plays a number of biological roles. As the adsorption of fibronectin onto the surface of implanted devices can lead to an inflammatory response or bacterial colonisation, understanding the interaction of fibronectin with material surfaces is important in the design of materials for biomedical applications. This, however, relies on having knowledge of the molecular-scale behaviour of proteins, which is difficult to investigate experimentally. In this paper, we used molecular dynamics simulations to investigate the adsorption of heparin-binding fibronectin domains onto hydrophobic surfaces. Despite the high similarity between these, their adsorption differs both in terms of the strength and the specificity of this, indicating that relatively small changes in protein structure can lead to significant changes in adsorption behaviour. This suggests that the interplay between protein structure and surface chemistry is vital for understanding the protein adsorption process and the design of novel biomaterials.
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(This article belongs to the Special Issue Protein Engineering: The Present and the Future 2.0)
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A Two-Species Finite Volume Scalar Model for Modeling the Diffusion of Poly(lactic-co-glycolic acid) into a Coronary Arterial Wall from a Single Half-Embedded Drug Eluting Stent Strut
Biophysica 2023, 3(2), 385-408; https://doi.org/10.3390/biophysica3020026 - 15 Jun 2023
Abstract
This paper outlines the methodology and results for a two-species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA)) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport
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This paper outlines the methodology and results for a two-species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA)) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two-species (free-drug and bound-drug) mass transport setup, including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of the drug between the free and bound-drug states. The model is solved by a 2D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over previously developed models using the finite-difference and finite element method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying the polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 h (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.
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(This article belongs to the Special Issue Molecular Structure and Simulation in Biological System)
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Computational Modeling of the Neurofibromin-Stimulated Guanosine Triphosphate Hydrolysis by the KRas Protein
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and
Biophysica 2023, 3(2), 373-384; https://doi.org/10.3390/biophysica3020025 - 31 May 2023
Cited by 1
Abstract
We report the results of computational studies of the guanosine triphosphate (GTP) hydrolysis in the active site of the KRas-NF1 protein complex, where KRas stands for the K-isoform of the Ras (ras sarcoma) protein and NF1 (neurofbromin-1) is the activating protein. The model
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We report the results of computational studies of the guanosine triphosphate (GTP) hydrolysis in the active site of the KRas-NF1 protein complex, where KRas stands for the K-isoform of the Ras (ras sarcoma) protein and NF1 (neurofbromin-1) is the activating protein. The model system was constructed using coordinates of heavy atoms from the crystal structure PDB ID 6OB2 with the GTP analog GMPPNP. Large-scale classical molecular dynamics (MD) calculations were performed to analyze conformations of the enzyme-substrate complexes. The Gibbs energy profiles for the hydrolysis reaction were computed using MD simulations with quantum mechanics/molecular mechanics (QM/MM) interaction potentials. The density functional theory DFT(ωB97X-D3/6-31G**) approach was applied in QM and the CHARMM36 force field parameters in MM. The most likely scenario of the chemical step of the GTP hydrolysis in KRas-NF1 corresponds to the water-assisted mechanism of the formation of the inorganic phosphate coupled with the dissociation of GTP to GDP.
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(This article belongs to the Special Issue Molecular Structure and Simulation in Biological System)
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