scholarly journals BION-2: Predicting Positions of Non-Specifically Bound Ions on Protein Surface by a Gaussian-Based Treatment of Electrostatics

2020 ◽  
Vol 22 (1) ◽  
pp. 272
Author(s):  
H. B. Mihiri Shashikala ◽  
Arghya Chakravorty ◽  
Shailesh Kumar Panday ◽  
Emil Alexov
Keyword(s):  
Thermal Fluctuation ◽  
Computational Method ◽  
Ion Concentration ◽  
Biological Processes ◽  
Poisson Boltzmann ◽  
Concentration Changes ◽  
Energy Of Interaction ◽  
Poisson Boltzmann Equation

Ions play significant roles in biological processes—they may specifically bind to a protein site or bind non-specifically on its surface. Although the role of specifically bound ions ranges from actively providing structural compactness via coordination of charge–charge interactions to numerous enzymatic activities, non-specifically surface-bound ions are also crucial to maintaining a protein’s stability, responding to pH and ion concentration changes, and contributing to other biological processes. However, the experimental determination of the positions of non-specifically bound ions is not trivial, since they may have a low residential time and experience significant thermal fluctuation of their positions. Here, we report a new release of a computational method, the BION-2 method, that predicts the positions of non-specifically surface-bound ions. The BION-2 utilizes the Gaussian-based treatment of ions within the framework of the modified Poisson–Boltzmann equation, which does not require a sharp boundary between the protein and water phase. Thus, the predictions are done by the balance of the energy of interaction between the protein charges and the corresponding ions and the de-solvation penalty of the ions as they approach the protein. The BION-2 is tested against experimentally determined ion’s positions and it is demonstrated that it outperforms the old BION and other available tools.

BION-2: Predicting Positions of Non-Specifically Bound ions on Protein Surface by a Gaussian-based Treatment of Electrostatic Environment

2020 ◽  
Author(s):  
Mihiri Shashikala ◽  
Arghya Chakravorty ◽  
Shailesh Pandey ◽  
Emil Alexov
Keyword(s):  
Thermal Fluctuation ◽  
Computational Method ◽  
Ion Concentration ◽  
Biological Processes ◽  
Poisson Boltzmann ◽  
Concentration Changes ◽  
Energy Of Interaction ◽  
Poisson Boltzmann Equation

Abstract Background: Ions play significant roles in biological processes - they may specifically bind to a protein site or bind non-specifically on its surface. Though, the role of specifically bound ions range from actively providing structural compactness via coordination of charge-charge interactions to numerous enzymatic activities, non-specifically surface-bound ions are also crucial to maintaining a protein’s stability, responding to pH and ion concentration changes and contributing to other biological processes. However, experimental determination of positions of non-specifically bound ions is not trivial since they may have low residential time and experience significant thermal fluctuation of their positions. Results: Here we report a new release of a computational method, the BION-2 method, that predicts positions of non-specifically surface-bound ions. The BION-2 utilizes the Gaussian-based treatment of ions within the framework of the modified Poisson-Boltzmann equation, that does not require a sharp boundary between the protein and water phase. Thus, the predictions are done by the balance of the energy of interaction between the protein charges and the corresponding ions, and the de-solvation penalty of the ions as they approach the protein. Conclusions: The BION-2 is tested against experimentally determined ion’s positions, with both X-ray and NMR determined positions, and it is demonstrated that it outperforms the old BION and molecular dynamics tools. The BION-2 is available as a web server as well.

scholarly journals Stability of unimolecular films of 32P-labelled lecithin

1967 ◽  
Vol 105 (1) ◽  
pp. 401-407 ◽  
Author(s):  
H. Hauser ◽  
R. M. C. Dawson
Keyword(s):  
Pressure Change ◽  
Ion Concentration ◽  
Hydrolysis Rate ◽  
Ion Distribution ◽  
Rapid Perfusion ◽  
Poisson Boltzmann ◽  
Rate Of Hydrolysis ◽  
Poisson Boltzmann Equation ◽  
The Stability ◽  
Hydrolysis Of

1. The stability of monolayers of a highly unsaturated yeast lecithin labelled with 32P has been investigated by a surface radioactivity technique. 2. Lecithin films on distilled water at all surface pressures between 6 and 48dynes/cm. were completely stable on rapid perfusion of the subphase and on addition of ionic amphipathic substances to the film. 3. Ultrasonically treated lecithin added to the subphase caused a slow loss of surface radioactivity but little pressure change. 4. The addition of proteins to the subphase caused negligible changes in the film even when conditions were favourable for electrostatic heterocoagulation and penetration. 5. Lecithin films were not hydrolysed by a strongly acid subphase at room temperature. The very low rate of hydrolysis produced by alkali was proportional to the subphase OH−ion concentration: the apparent activation energy and temperature coefficient (Q10) of the reaction were 14250 cal. and 2·37 respectively. 6. Alkaline hydrolysis of lecithin monolayers was markedly stimulated by adding methanol (10–20%, v/v) to the subphase. The addition of ionic amphipaths to the monolayer had the expected type of effect on the hydrolysis rate, but its magnitude was far less than that suggested by an application of the Poisson–Boltzmann equation for ion distribution at a charged interface (Davies & Rideal, 1963).

scholarly journals Reliable Computer Simulation Methods for Electrostatic Biomolecular Models Based on the Poisson–Boltzmann Equation

2020 ◽  
Vol 20 (4) ◽  
pp. 643-676 ◽  
Author(s):  
Johannes Kraus ◽  
Svetoslav Nakov ◽  
Sergey Repin
Keyword(s):  
Boltzmann Equation ◽  
Numerical Solution ◽  
Real Life ◽  
Generalized Solution ◽  
Normal Derivative ◽  
Computational Method ◽  
Weak Formulation ◽  
Poisson Boltzmann ◽  
The Difference ◽  
Poisson Boltzmann Equation

AbstractThe paper is concerned with the reliable numerical solution of a class of nonlinear interface problems governed by the Poisson–Boltzmann equation. Arising in electrostatic biomolecular models these problems typically contain measure-type source terms and their solution often exposes drastically different behaviour in different subdomains. The interface conditions reflect the requirement that the potential and its normal derivative must be continuous. In the first part of the paper, we discuss an appropriate weak formulation of the problem that guarantees existence and uniqueness of the generalized solution. In the context of the considered class of nonlinear equations, this question is not trivial and requires additional analysis, which is based on a special splitting of the problem into simpler subproblems whose weak solutions can be defined in standard Sobolev spaces. This splitting also suggests a rational numerical solution strategy and a way of deriving fully guaranteed error bounds. These bounds (error majorants) are derived for each subproblem separately and, finally, yield a fully computable majorant of the difference between the exact solution of the original problem and any energy-type approximation of it.The efficiency of the suggested computational method is verified in a series of numerical tests related to real-life biophysical systems.

scholarly journals De novo determination of near-surface electrostatic potentials by NMR

2021 ◽  
Vol 118 (25) ◽  
pp. e2104020118
Author(s):  
Binhan Yu ◽  
Channing C. Pletka ◽  
B. Montgomery Pettitt ◽  
Junji Iwahara
Keyword(s):  
De Novo ◽  
Structural Information ◽  
Electrostatic Potentials ◽  
Biological Macromolecules ◽  
Near Surface ◽  
Nmr Method ◽  
Surface Electrostatic Potentials ◽  
Poisson Boltzmann ◽  
Poisson Boltzmann Equation

Electrostatic potentials computed from three-dimensional structures of biomolecules by solving the Poisson–Boltzmann equation are widely used in molecular biophysics, structural biology, and medicinal chemistry. Despite the approximate nature of the Poisson–Boltzmann theory, validation of the computed electrostatic potentials around biological macromolecules is rare and methodologically limited. Here, we present a unique and powerful NMR method that allows for straightforward and extensive comparison with electrostatic models for biomolecules and their complexes. This method utilizes paramagnetic relaxation enhancement arising from analogous cationic and anionic cosolutes whose spatial distributions around biological macromolecules reflect electrostatic potentials. We demonstrate that this NMR method enables de novo determination of near-surface electrostatic potentials for individual protein residues without using any structural information. We applied the method to ubiquitin and the Antp homeodomain–DNA complex. The experimental data agreed well with predictions from the Poisson–Boltzmann theory. Thus, our experimental results clearly support the validity of the theory for these systems. However, our experimental study also illuminates certain weaknesses of the Poisson–Boltzmann theory. For example, we found that the theory predicts stronger dependence of near-surface electrostatic potentials on ionic strength than observed in the experiments. Our data also suggest that conformational flexibility or structural uncertainties may cause large errors in theoretical predictions of electrostatic potentials, particularly for highly charged systems. This NMR-based method permits extensive assessment of near-surface electrostatic potentials for various regions around biological macromolecules and thereby may facilitate improvement of the computational approaches for electrostatic potentials.

scholarly journals Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

2021 ◽  
Vol 22 (5) ◽  
pp. 2661
Author(s):  
Małgorzata Prokopowicz ◽  
Adam Jarmuła ◽  
Yannick Casamayou-Boucau ◽  
Fiona Gordon ◽  
Alan Ryder ◽  
...  
Keyword(s):  
Electrostatic Potential ◽  
Thymidylate Synthase ◽  
Wild Type Mouse ◽  
Inhibitory Mechanism ◽  
Wild Type ◽  
Theoretical Investigations ◽  
Ligand Interactions ◽  
Poisson Boltzmann

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

ІНТЕРПРЕТАЦІЯ КАТЕГОРІЇ РОЗВИТКУ В СУЧАСНІЙ ПСИХОЛОГІЇ

1970 ◽  
Vol 8 (1) ◽  
pp. 22-30
Author(s):  
Анжеліка Шамне
Keyword(s):  
Cultural Context ◽  
Developmental Psychology ◽  
Structure And Dynamics ◽  
Modern Psychology ◽  
Development Site ◽  
Approaches To Study ◽  
Methodological Approaches ◽  
Self Motion

У статті розглянуто сучасні підходи до інтерпретації категорії розвитку, розкрито теоретичні  та методологічні підходи до вивчення категорії розвитку у сучасній психології, визначено її психологічний  зміст,   моделі,   структуру   та   динаміку.   Категорія   розвитку   розглядається   як   епіцентр   наукової  проблематики у психології та як поняття інтегративного типу. Розвиток проаналізовано як категорію,  явище і проблему психології розвитку в різних аспектах аналізу. Розглянуто місце розвитку в системі  споріднених психологічних понять. У статті також аналізуються психологічні аспекти теоретичних та  методологічних  постнекласичних  тенденцій  вивчення  природи,  характеру  та  визначення  психічного  розвитку. Постнекласична парадигма та плюралістична методологія пізнання визначають розмитість  дисциплінарної мови  та  врахування  ролі  соціокультурного  контексту  при  вивченні  психологічних явищ.  Важливими тенденціями сучасного теоретико-методологічного стану психологічних досліджень розвитку  також є визнання неефективності моністичного підходу до його вивчення, взаємозв'язок теоретичних ідей  та   спроби   створення   метатеоретичних   схем,   постнекласичне   розуміння   розвитку   як   принципово  незавершеного   процесу   саморуху,   актуалізація   антропологічного   діапазону   проблем   та   посилення  спрямованості на роль культурного контексту в дослідженні розвитку людини.  The article deals with the modern approaches to the interpretation of the category of development, reveals  the theoretical and methodological approaches to study of development in modern psychology, its psychological  content, patterns, structure and dynamics. Category of development is viewed as an epicenter of scientific issues in  modern  psychology  and  the  concept  of  the  integrative  type.  Category  of  development  is  considered  as  the  phenomenon  and  the  problem  of  developmental  psychology  in  various  aspects  of  the  analysis.  Analyzed  the  development site in the related psychological concepts. The article analyzes the psychological aspects of theoretical  and methodological postnonclassical contemporary trends in the study of nature, character, and determination of  mental  development.  Postnonclassical  paradigm  and  pluralistic  methodology  of  knowledge  determine  the  disciplinary blurring and increase of the role of the analysis of socio-cultural context in the study of psychological  phenomenon. The important tendencies of modern theoretical and methodological state of psychological researches  of development are facts of inefficiency of the monistic approach to its study, interconnection of theoretical ideas  and   attempts   of  creating   metatheoretical   schemes,   postnonclassical   understanding   of   development   as   a  fundamentally  uncompleted  process  of  self-motion,  actualization  of  anthropological  range  of  problems  and  strengthening of focus on the role of cultural context in research of human development.   

Role of the family focused technologies in the clinical course of pregnancy at women of high obstetric risk

2016 ◽  
pp. 64-66
Author(s):  
S.Yu. Vdovichenko ◽  
Keyword(s):  
Comparison Group ◽  
Traditional Approach ◽  
Married Couple ◽  
Premature Births ◽  
Individual Support ◽  
The Family ◽  
Risk Patients ◽  
Individual Preparation

The objective: to show a role of the family focused technologies in depression of frequency of pathology of pregnancy at women of high obstetric risk. Patients and methods. For determination of efficiency of prophylaxis of pathology of pregnancy on the basis of use of the family focused technologies complex clinical-psychological and laboratory and tool examination of 300 women with factors of obstetric risk which were divided into two groups was conducted. In the main group – 182 women with motivation on partner labors to which provided training on system of individual preparation of married couple to labors. The comparison group consisted of 118 women who were not in prenatal training and had individual support in childbirth, with the traditional approach to pain management. Results. Use of the family focused technologies during pregnancy allows to reduce significantly the frequency of the main complications of pregnancy, especially not incubation and premature births. Conclusion. In our opinion, the technique is simple, available and can widely be used in practical health care at women with high obstetric risk. Key words: obstetric risk, the family focused technologies, prophylaxis.

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