Pub Date : 2022-11-17DOI: 10.3390/biophysica2040041
E. Alizadeh, Dipayan Chakraborty, S. Ptasińska
Technological advancement has produced a variety of instruments and methods to generate electron beams that have greatly assisted in the extensive theoretical and experimental efforts devoted to investigating the effect of secondary electrons with energies approximately less than 100 eV, which are referred as low-energy electrons (LEEs). In the past two decades, LEE studies have focused on biomolecular systems, which mainly consist of DNA and proteins and their constituents as primary cellular targets of ionizing radiation. These studies have revealed that compared to other reactive species produced by high-energy radiation, LEEs have distinctive pathways and considerable efficiency in inducing lethal DNA lesions. The present work aims to briefly discuss the current state of LEE production technology and to motivate further studies and improvements of LEE generation techniques in relation to biological electron-driven processes associated with such medical applications as radiation therapy and cancer treatment.
{"title":"Low-Energy Electron Generation for Biomolecular Damage Inquiry: Instrumentation and Methods","authors":"E. Alizadeh, Dipayan Chakraborty, S. Ptasińska","doi":"10.3390/biophysica2040041","DOIUrl":"https://doi.org/10.3390/biophysica2040041","url":null,"abstract":"Technological advancement has produced a variety of instruments and methods to generate electron beams that have greatly assisted in the extensive theoretical and experimental efforts devoted to investigating the effect of secondary electrons with energies approximately less than 100 eV, which are referred as low-energy electrons (LEEs). In the past two decades, LEE studies have focused on biomolecular systems, which mainly consist of DNA and proteins and their constituents as primary cellular targets of ionizing radiation. These studies have revealed that compared to other reactive species produced by high-energy radiation, LEEs have distinctive pathways and considerable efficiency in inducing lethal DNA lesions. The present work aims to briefly discuss the current state of LEE production technology and to motivate further studies and improvements of LEE generation techniques in relation to biological electron-driven processes associated with such medical applications as radiation therapy and cancer treatment.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45482525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-17DOI: 10.3390/biophysica2040040
G. Cottone, A. Cupane, M. Leone, V. Vetri, V. Militello
An overview of the biophysics activity at the Department of Physics and Chemistry Emilio Segrè of the University of Palermo is given. For forty years, the focus of the research has been on the protein structure–dynamics–function paradigm, with the aim of understanding the molecular basis of the relevant mechanisms and the key role of solvent. At least three research lines are identified; the main results obtained in collaboration with other groups in Italy and abroad are presented. This review is dedicated to the memory of Professors Massimo Ugo Palma, Maria Beatrice Palma Vittorelli, and Lorenzo Cordone, which were the founders of the Palermo School of Biophysics. We all have been, directly or indirectly, their pupils; we miss their enthusiasm for scientific research, their deep physical insights, their suggestions, their strict but always constructive criticisms, and, most of all, their friendship. This paper is dedicated also to the memory of Prof. Hans Frauenfelder, whose pioneering works on nonexponential rebinding kinetics, protein substates, and energy landscape have inspired a large part of our work in the field of protein dynamics.
{"title":"A Long Journey into the Investigation of the Structure–Dynamics–Function Paradigm in Proteins through the Activities of the Palermo Biophysics Group","authors":"G. Cottone, A. Cupane, M. Leone, V. Vetri, V. Militello","doi":"10.3390/biophysica2040040","DOIUrl":"https://doi.org/10.3390/biophysica2040040","url":null,"abstract":"An overview of the biophysics activity at the Department of Physics and Chemistry Emilio Segrè of the University of Palermo is given. For forty years, the focus of the research has been on the protein structure–dynamics–function paradigm, with the aim of understanding the molecular basis of the relevant mechanisms and the key role of solvent. At least three research lines are identified; the main results obtained in collaboration with other groups in Italy and abroad are presented. This review is dedicated to the memory of Professors Massimo Ugo Palma, Maria Beatrice Palma Vittorelli, and Lorenzo Cordone, which were the founders of the Palermo School of Biophysics. We all have been, directly or indirectly, their pupils; we miss their enthusiasm for scientific research, their deep physical insights, their suggestions, their strict but always constructive criticisms, and, most of all, their friendship. This paper is dedicated also to the memory of Prof. Hans Frauenfelder, whose pioneering works on nonexponential rebinding kinetics, protein substates, and energy landscape have inspired a large part of our work in the field of protein dynamics.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45387826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-11DOI: 10.3390/biophysica2040039
Chih Hung Lo
Tauopathies, including Alzheimer’s disease (AD), are a group of neurodegenerative disorders characterized by pathological aggregation of microtubule binding protein tau. The presence of tau neurofibrillary tangles, which are insoluble β-sheet fibrils, in the brain has been the histopathological hallmark of these diseases as their level correlates with the degree of cognitive impairment. However, recent studies suggest that tau oligomers, which are soluble proteins that are formed prior to insoluble fibrils, are the principal toxic species impairing neurons and inducing neurodegeneration. Targeting toxic tau oligomers is challenging, as they are mostly unstructured and adopting multiple conformations. The heterogeneity of tau oligomers is further illustrated by the different oligomeric species formed by various methods. The current models and technologies to study tau oligomerization represent important resources and avenues to push the forefront of elucidating the true toxic tau species. In this review, we will summarize the distinct tau oligomers generated using different strategies and discuss their conformational characteristics, neurotoxicity, relevance to pathological phenotypes, as well as their applications in drug discovery. This information will provide insights to understanding heterogeneous tau oligomers and their role as molecular targets for AD and related tauopathies.
{"title":"Heterogeneous Tau Oligomers as Molecular Targets for Alzheimer’s Disease and Related Tauopathies","authors":"Chih Hung Lo","doi":"10.3390/biophysica2040039","DOIUrl":"https://doi.org/10.3390/biophysica2040039","url":null,"abstract":"Tauopathies, including Alzheimer’s disease (AD), are a group of neurodegenerative disorders characterized by pathological aggregation of microtubule binding protein tau. The presence of tau neurofibrillary tangles, which are insoluble β-sheet fibrils, in the brain has been the histopathological hallmark of these diseases as their level correlates with the degree of cognitive impairment. However, recent studies suggest that tau oligomers, which are soluble proteins that are formed prior to insoluble fibrils, are the principal toxic species impairing neurons and inducing neurodegeneration. Targeting toxic tau oligomers is challenging, as they are mostly unstructured and adopting multiple conformations. The heterogeneity of tau oligomers is further illustrated by the different oligomeric species formed by various methods. The current models and technologies to study tau oligomerization represent important resources and avenues to push the forefront of elucidating the true toxic tau species. In this review, we will summarize the distinct tau oligomers generated using different strategies and discuss their conformational characteristics, neurotoxicity, relevance to pathological phenotypes, as well as their applications in drug discovery. This information will provide insights to understanding heterogeneous tau oligomers and their role as molecular targets for AD and related tauopathies.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48141220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-03DOI: 10.3390/biophysica2040037
M. Bleszynski
Various alternative compounds have been investigated to prevent icing, one of which includes poly(vinyl) alcohol (PVA), which has shown promising anti-freeze effects. However, determining the optimal structures and formulations of PVA for anti-icing applications has remained a challenge. Building upon our previous work, which used molecular dynamics simulations to assess the effects of hydroxyl group separation distance on ice nucleation, in this work, PVA was modified based upon the structures of antifreeze glycoproteins (AFGPs) found in Antarctic fish, and examined as a potential antifreeze compound. Four different PVA samples with different degrees of hydrolysis were fabricated and subsequently examined for their effects on ice crystallization. The results showed that the modified PVA samples with degrees of hydrolysis of 76% and 66% had an effect on ice crystallization, delaying ice crystallization by an average of approximately 20 min, and even preventing ice crystallization altogether in a small portion of the sample. Meanwhile, other samples with degrees of hydrolysis of 100% and 34% either showed no effect on ice crystallization, shortened the ice crystallization time, and appeared to promote ice nucleation.
{"title":"The Modification of Polyvinyl Alcohol for Ice Nucleation Based upon the Structures of Antifreeze Glycoproteins Found in Antarctic Fish","authors":"M. Bleszynski","doi":"10.3390/biophysica2040037","DOIUrl":"https://doi.org/10.3390/biophysica2040037","url":null,"abstract":"Various alternative compounds have been investigated to prevent icing, one of which includes poly(vinyl) alcohol (PVA), which has shown promising anti-freeze effects. However, determining the optimal structures and formulations of PVA for anti-icing applications has remained a challenge. Building upon our previous work, which used molecular dynamics simulations to assess the effects of hydroxyl group separation distance on ice nucleation, in this work, PVA was modified based upon the structures of antifreeze glycoproteins (AFGPs) found in Antarctic fish, and examined as a potential antifreeze compound. Four different PVA samples with different degrees of hydrolysis were fabricated and subsequently examined for their effects on ice crystallization. The results showed that the modified PVA samples with degrees of hydrolysis of 76% and 66% had an effect on ice crystallization, delaying ice crystallization by an average of approximately 20 min, and even preventing ice crystallization altogether in a small portion of the sample. Meanwhile, other samples with degrees of hydrolysis of 100% and 34% either showed no effect on ice crystallization, shortened the ice crystallization time, and appeared to promote ice nucleation.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41829442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-01DOI: 10.3390/biophysica2040036
D. Prikule, V. Kukushkin, V. F. Prikuls
This study shows that the luminescent diagnostic of oral fluid allows the determination of the severity of inflammatory markers after implantation. The noninvasive diagnostic method, which is used, allows the rapid detection of the stages of development of the inflammatory process after intraosseous implantation and prevents the development of complications in the postoperative period.
{"title":"Noninvasive Digital Method for Determining Inflammation after Dental Implantation","authors":"D. Prikule, V. Kukushkin, V. F. Prikuls","doi":"10.3390/biophysica2040036","DOIUrl":"https://doi.org/10.3390/biophysica2040036","url":null,"abstract":"This study shows that the luminescent diagnostic of oral fluid allows the determination of the severity of inflammatory markers after implantation. The noninvasive diagnostic method, which is used, allows the rapid detection of the stages of development of the inflammatory process after intraosseous implantation and prevents the development of complications in the postoperative period.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46327786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-28DOI: 10.3390/biophysica2040035
A. Sedigh, M. Akbarzadeh-T., R. Tomlinson
Bioprinting is an emerging tissue engineering method used to generate cell-laden scaffolds with high spatial resolution. Bioprinting parameters, such as pressure, nozzle size, and speed, highly influence the quality of the bioprinted construct. Moreover, cell suspension density and other critical biological parameters directly impact the biological function. Therefore, an approximation model that can be used to find the optimal bioprinting parameter settings for bioprinted constructs is highly desirable. Here, we propose a type-2 fuzzy model to handle the uncertainty and imprecision in the approximation model. Specifically, we focus on the biological parameters, such as the culture period, that can be used to maximize the output value (mineralization volume 21.8 mm3 with the same culture period of 21 days). We have also implemented a type-1 fuzzy model and compared the results with the proposed type-2 fuzzy model using two levels of uncertainty. We hypothesize that the type-2 fuzzy model may be preferred in biological systems due to the inherent vagueness and imprecision of the input data. Our numerical results confirm this hypothesis. More specifically, the type-2 fuzzy model with a high uncertainty boundary (30%) is superior to type-1 and type-2 fuzzy systems with low uncertainty boundaries in the overall output approximation error for bone bioprinting inputs.
{"title":"Optimizing Mineralization of Bioprinted Bone Utilizing Type-2 Fuzzy Systems","authors":"A. Sedigh, M. Akbarzadeh-T., R. Tomlinson","doi":"10.3390/biophysica2040035","DOIUrl":"https://doi.org/10.3390/biophysica2040035","url":null,"abstract":"Bioprinting is an emerging tissue engineering method used to generate cell-laden scaffolds with high spatial resolution. Bioprinting parameters, such as pressure, nozzle size, and speed, highly influence the quality of the bioprinted construct. Moreover, cell suspension density and other critical biological parameters directly impact the biological function. Therefore, an approximation model that can be used to find the optimal bioprinting parameter settings for bioprinted constructs is highly desirable. Here, we propose a type-2 fuzzy model to handle the uncertainty and imprecision in the approximation model. Specifically, we focus on the biological parameters, such as the culture period, that can be used to maximize the output value (mineralization volume 21.8 mm3 with the same culture period of 21 days). We have also implemented a type-1 fuzzy model and compared the results with the proposed type-2 fuzzy model using two levels of uncertainty. We hypothesize that the type-2 fuzzy model may be preferred in biological systems due to the inherent vagueness and imprecision of the input data. Our numerical results confirm this hypothesis. More specifically, the type-2 fuzzy model with a high uncertainty boundary (30%) is superior to type-1 and type-2 fuzzy systems with low uncertainty boundaries in the overall output approximation error for bone bioprinting inputs.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47000333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-27DOI: 10.3390/biophysica2040034
Ariadna Villanueva, Henry Secaira-Morocho, L. F. Seoane, E. Lázaro, S. Manrubia
Viral populations are large and highly heterogeneous. Despite the evolutionary relevance of such heterogeneity, statistical approaches to quantifying the extent to which viruses maintain a high genotypic and/or phenotypic diversity have been rarely pursued. Here, we address this issue by analyzing a nucleotide-to-protein sequence map through deep sequencing of populations of the Qβ phage adapted to high temperatures. Tens of thousands of different sequences corresponding to two fragments of the gene coding for the viral replicase were recovered. A diversity analysis of two independent populations consistently revealed that about 40% of the mutations identified caused changes in protein amino acids, leading to an almost complete exploration of the protein neighborhood of (non-silent) mutants at a distance of one. The functional form of the empirical distribution of phenotype abundance agreed with analytical calculations that assumed random mutations in the nucleotide sequence. Our results concur with the idea that viral populations maintain a high diversity as an efficient adaptive mechanism and support the hypothesis of universality for a lognormal distribution of phenotype abundances in biologically meaningful genotype–phenotype maps, highlighting the relevance of entropic effects in molecular evolution.
{"title":"Genotype-to-Protein Map and Collective Adaptation in a Viral Population","authors":"Ariadna Villanueva, Henry Secaira-Morocho, L. F. Seoane, E. Lázaro, S. Manrubia","doi":"10.3390/biophysica2040034","DOIUrl":"https://doi.org/10.3390/biophysica2040034","url":null,"abstract":"Viral populations are large and highly heterogeneous. Despite the evolutionary relevance of such heterogeneity, statistical approaches to quantifying the extent to which viruses maintain a high genotypic and/or phenotypic diversity have been rarely pursued. Here, we address this issue by analyzing a nucleotide-to-protein sequence map through deep sequencing of populations of the Qβ phage adapted to high temperatures. Tens of thousands of different sequences corresponding to two fragments of the gene coding for the viral replicase were recovered. A diversity analysis of two independent populations consistently revealed that about 40% of the mutations identified caused changes in protein amino acids, leading to an almost complete exploration of the protein neighborhood of (non-silent) mutants at a distance of one. The functional form of the empirical distribution of phenotype abundance agreed with analytical calculations that assumed random mutations in the nucleotide sequence. Our results concur with the idea that viral populations maintain a high diversity as an efficient adaptive mechanism and support the hypothesis of universality for a lognormal distribution of phenotype abundances in biologically meaningful genotype–phenotype maps, highlighting the relevance of entropic effects in molecular evolution.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45362310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-26DOI: 10.3390/biophysica2040033
P. Serwer, E. Wright
Chemotherapy-inhibiting tumor cell evolution to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible increase in tumor-delivered drug dose, which would suppress opportunities to evolve drug resistance. Currently used DDVs do not have gating but gating is a natural feature of some bacteriophages (phages). Phage T4, which has recently been found highly persistent in murine blood, is a potential gated DDV. Thus, here, we proceed towards a T4-DDV by developing (1) improved procedure for generating high concentrations and amounts of phage T4, (2) elevated temperature-driven gate-opening and ethidium- and bleomycin-loading, and (3) purification of loaded T4 by rate zonal centrifugation. We test for loading by native agarose gel electrophoresis (AGE) with fluorescence detection. We observe loading in both phage T4 and T4 (tail-free) heads. The loaded particles have an openable, closed gate. Stored, mature T4 phages and phage heads do not release ethidium during at least a month at 4 °C and 6 days at 37 and 42 °C. Tumor-specific T4 phage delivery is projected via both the EPR effect and high T4 persistence.
{"title":"Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free","authors":"P. Serwer, E. Wright","doi":"10.3390/biophysica2040033","DOIUrl":"https://doi.org/10.3390/biophysica2040033","url":null,"abstract":"Chemotherapy-inhibiting tumor cell evolution to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible increase in tumor-delivered drug dose, which would suppress opportunities to evolve drug resistance. Currently used DDVs do not have gating but gating is a natural feature of some bacteriophages (phages). Phage T4, which has recently been found highly persistent in murine blood, is a potential gated DDV. Thus, here, we proceed towards a T4-DDV by developing (1) improved procedure for generating high concentrations and amounts of phage T4, (2) elevated temperature-driven gate-opening and ethidium- and bleomycin-loading, and (3) purification of loaded T4 by rate zonal centrifugation. We test for loading by native agarose gel electrophoresis (AGE) with fluorescence detection. We observe loading in both phage T4 and T4 (tail-free) heads. The loaded particles have an openable, closed gate. Stored, mature T4 phages and phage heads do not release ethidium during at least a month at 4 °C and 6 days at 37 and 42 °C. Tumor-specific T4 phage delivery is projected via both the EPR effect and high T4 persistence.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47810379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-17DOI: 10.3390/biophysica2040032
I. Le-Deygen, A. Safronova, P. Mamaeva, I. Kolmogorov, A. Skuredina, E. Kudryashova
We have investigated the nature of the interaction of small organic drug molecules with lipid membranes of various compositions. Using infrared spectroscopy and differential scanning calorimetry methods, we studied the role of the structure of the active molecule in interaction with the membrane using the example of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylcholine:cardiolipin (DPPC:CL) liposomes. We discovered the key role of the heterocycle in interaction with the polar part of the bilayer and the network of unsaturated bonds in interaction with the hydrophobic part. For rifampicin and levofloxacin, the main binding sites were phosphate and carbonyl groups of lipids, and in the case of anionic liposomes we found a slight penetration of rifampicin into the hydrophobic part of the bilayer. For rapamycin, experimental confirmation of the localization of the molecule in the region of fatty acid chains was obtained, and perturbation in the region of phosphate groups was demonstrated for the first time. The process of phase transition of liposomal forms of rifampicin and levofloxacin was studied. DPPC liposomes accelerate the phase transition when loaded with a drug. DPPC:CL liposomes are less susceptible to changes in the phase transition rate.
{"title":"Drug–Membrane Interaction as Revealed by Spectroscopic Methods: The Role of Drug Structure in the Example of Rifampicin, Levofloxacin and Rapamycin","authors":"I. Le-Deygen, A. Safronova, P. Mamaeva, I. Kolmogorov, A. Skuredina, E. Kudryashova","doi":"10.3390/biophysica2040032","DOIUrl":"https://doi.org/10.3390/biophysica2040032","url":null,"abstract":"We have investigated the nature of the interaction of small organic drug molecules with lipid membranes of various compositions. Using infrared spectroscopy and differential scanning calorimetry methods, we studied the role of the structure of the active molecule in interaction with the membrane using the example of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylcholine:cardiolipin (DPPC:CL) liposomes. We discovered the key role of the heterocycle in interaction with the polar part of the bilayer and the network of unsaturated bonds in interaction with the hydrophobic part. For rifampicin and levofloxacin, the main binding sites were phosphate and carbonyl groups of lipids, and in the case of anionic liposomes we found a slight penetration of rifampicin into the hydrophobic part of the bilayer. For rapamycin, experimental confirmation of the localization of the molecule in the region of fatty acid chains was obtained, and perturbation in the region of phosphate groups was demonstrated for the first time. The process of phase transition of liposomal forms of rifampicin and levofloxacin was studied. DPPC liposomes accelerate the phase transition when loaded with a drug. DPPC:CL liposomes are less susceptible to changes in the phase transition rate.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48129022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-13DOI: 10.3390/biophysica2040031
Roberto Borelli, A. Dovier, F. Fogolari
Entropy of multivariate distributions may be estimated based on the distances of nearest neighbours from each sample from a statistical ensemble. This technique has been applied on biomolecular systems for estimating both conformational and translational/rotational entropy. The degrees of freedom which mostly define conformational entropy are torsion angles with their periodicity. In this work, tree structures and algorithms to quickly generate lists of nearest neighbours for periodic and non-periodic data are reviewed and applied to biomolecular conformations as described by torsion angles. The effect of dimensionality, number of samples, and number of neighbours on the computational time is assessed. The main conclusion is that using proper data structures and algorithms can greatly reduce the complexity of nearest neighbours lists generation, which is the bottleneck step in nearest neighbours entropy estimation.
{"title":"Data Structures and Algorithms for k-th Nearest Neighbours Conformational Entropy Estimation","authors":"Roberto Borelli, A. Dovier, F. Fogolari","doi":"10.3390/biophysica2040031","DOIUrl":"https://doi.org/10.3390/biophysica2040031","url":null,"abstract":"Entropy of multivariate distributions may be estimated based on the distances of nearest neighbours from each sample from a statistical ensemble. This technique has been applied on biomolecular systems for estimating both conformational and translational/rotational entropy. The degrees of freedom which mostly define conformational entropy are torsion angles with their periodicity. In this work, tree structures and algorithms to quickly generate lists of nearest neighbours for periodic and non-periodic data are reviewed and applied to biomolecular conformations as described by torsion angles. The effect of dimensionality, number of samples, and number of neighbours on the computational time is assessed. The main conclusion is that using proper data structures and algorithms can greatly reduce the complexity of nearest neighbours lists generation, which is the bottleneck step in nearest neighbours entropy estimation.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43781683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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