scholarly journals Structural Consequences of the Villin Headpiece Interaction with a Carbon Nitride Polyaniline (C3N) Nanosheet

2020 ◽  
Author(s):  
Zonglin Gu ◽  
Jose Manuel Perez-Aguilar ◽  
Ruhong Zhou
Keyword(s):  
Interaction Energy ◽  
Protein C ◽  
Biomedical Applications ◽  
Carbon Nitride ◽  
Md Simulations ◽  
Limited Information ◽  
Villin Headpiece ◽  
Partial Denaturation ◽  
Living Tissues ◽  
Shed Light

ABSTRACTCarbon nitride polyaniline (C3N) nanosheets shared a similar structure with graphene and have been utilized in biomedical applications since its recent successful synthesis. However, limited information was known about the interaction of this next-generation nanomaterial with biomolecules, which might hamper its applications in living tissues. Here, by using all-atom molecular dynamics (MD) simulations, we investigated the interaction between a C3N nanosheet and the prototypical protein villin headpiece (HP35), in order to identify the mechanistic determinants of such interaction; this knowledge will provide guidelines about C3N’s biocompatibility. Our MD simulations revealed that the C3N-based nanomaterial caused the partial denaturation of HP35 once the protein was bound on its surface. That is, upon adsorption, we observed the loss of the protein’s interior hydrogen bonds and the native contacts, which were related with unwinding events in the protein’s helices. The protein/C3N nanosheet interacting process was dominated by vdW contributions to the energy and the stepwise changes observed in the values of this energy term suggested a gradual unfolding pattern of HP35 during the absorption event. Furthermore, we also found that the interaction energy showed a linear correlation with the native Q ratio of HP35, suggesting that the degree of HP35 unfolding was linearly time-dependent to the interaction energy. Our findings shed light on the underlying molecular mechanism of the potential consequences of C3N-based nanostructures to proteins, which might delineate the future applications of these nanomaterials in biomedicine.

Partial Denaturation of Villin Headpiece upon Binding to a Carbon Nitride Polyaniline (C3N) Nanosheet

2020 ◽  
Vol 124 (35) ◽  
pp. 7557-7563
Author(s):  
Zonglin Gu ◽  
Jose Manuel Perez-Aguilar ◽  
Lijun Meng ◽  
Ruhong Zhou
Keyword(s):  
Carbon Nitride ◽  
Villin Headpiece ◽  
Partial Denaturation

scholarly journals Spectroscopic BIL-SFG Invariance Hides the Chaotropic Effect of Protons at the Air-Water Interface

Atmosphere ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 396 ◽  
Author(s):  
Simone Pezzotti ◽  
Marie-Pierre Gaigeot
Keyword(s):  
Water Structure ◽  
Md Simulations ◽  
Interfacial Structure ◽  
Water Interface ◽  
Sum Frequency ◽  
Hydronium Ion ◽  
Sum Frequency Generation Spectroscopy ◽  
Air Water Interface ◽  
Ph Conditions ◽  
Shed Light

The knowledge of the water structure at the interface with the air in acidic pH conditions is of utmost importance for chemistry in the atmosphere. We shed light on the acidic air-water (AW) interfacial structure by DFT-MD simulations of the interface containing one hydronium ion coupled with theoretical SFG (Sum Frequency Generation) spectroscopy. The interpretation of SFG spectra at charged interfaces requires a deconvolution of the signal into BIL (Binding Interfacial Layer) and DL (Diffuse Layer) SFG contributions, which is achieved here, and hence reveals that even though H 3 O + has a chaotropic effect on the BIL water structure (by weakening the 2D-HBond-Network observed at the neat air-water interface) it has no direct probing in SFG spectroscopy. The changes observed experimentally in the SFG of the acidic AW interface from the SFG at the neat AW are shown here to be solely due to the DL-SFG contribution to the spectroscopy. Such BIL-SFG and DL-SFG deconvolution rationalizes the experimental SFG data in the literature, while the hydronium chaotropic effect on the water 2D-HBond-Network in the BIL can be put in perspective of the decrease in surface tension at acidic AW interfaces.

Emerging graphitic carbon nitride-based materials for biomedical applications

2020 ◽  
Vol 112 ◽  
pp. 100666 ◽  
Author(s):  
Guangfu Liao ◽  
Fei He ◽  
Qing Li ◽  
Liu Zhong ◽  
Ruizheng Zhao ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Carbon Nitride ◽  
Graphitic Carbon ◽  
Graphitic Carbon Nitride

scholarly journals Differential Effects of Anti–β2-Glycoprotein I and Antiprothrombin Antibodies on the Anticoagulant Activity of Activated Protein C

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 1999-2004 ◽  
Author(s):  
Monica Galli ◽  
Luisa Ruggeri ◽  
Tiziano Barbui
Keyword(s):  
Protein C ◽  
Time Course ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Limited Information ◽  
Coagulation Profile ◽  
Glycoprotein I ◽  
Increased Risk ◽  
Antiprothrombin Antibodies ◽  
Normal Controls

Abstract Antiprothrombin and anti–β2-glycoprotein I (β2-GPI) antibodies belong to the family of antiphospholipid (APL) antibodies and represent the phospholipid-dependent inhibitors of coagulation. They may be distinguished by analyzing the coagulation profiles generated by the comparison of the ratios of two coagulation tests, the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT), commonly adopted for their diagnosis. The KCT profile is caused by antiprothrombin antibodies, whereas anti–β2-GPI antibodies are responsible for the dRVVT coagulation profile. The presence of aPL antibodies is frequently associated with acquired resistance to activated Protein C (APC-R), but limited information is available regarding the role of the different antibodies in its development. We studied the time-course of activated Factor V (FVa) generation and inactivation in the plasma of 42 patients with well-defined phospholipid-dependent inhibitors of coagulation: 24 displayed the dRVVT coagulation profile, whereas the other 18 cases showed the KCT profile. In normal pooled plasma, the peak values of FVa (mean ± standard deviation, [SD]: 16.307 ± 4.372 U/mL) were reached in 4 to 5 minutes and an almost complete inactivation (0.088 ± 0.123 U/mL) was obtained within 20 minutes. At this time point, values of residual FVa exceeding 2 SD the mean of controls (0.344 U/mL) were considered abnormal. Patients belonging to the KCT coagulation profile group reached the maximal amount of FVa in plasma (22.740 ± 7.693 U/mL, P = not significant v controls) within 4 to 5 minutes; at 20 minutes, the residual amount of FVa in plasma ranged from 0 to 1.09 U/mL (0.293 ± 0.298; P = .027), but it was found abnormal in only six of the 18 cases. The time-course of FVa in plasma of patients belonging to the dRVVT coagulation profile group differed from that of normal controls in that the peak values (10.955 ± 5.092 U/mL) were reached at 10 minutes and the amount of residual FVa at 20 minutes ranged from 0.320 to 14.450 U/ml (2.544 ± 3.580 U/mL;P = .0191 v normal controls and P = .0114v KCT group patients). Twenty of the 24 patients belonging to the dRVVT profile group had an abnormal inactivation of FVa (χ2 = 0.001 v KCT group patients). History of venous thrombosis was experienced by 15 patients: an abnormal rate of FVa inactivation was found in 11 of them (73%) versus 15 of the 27 cases without thrombosis (56%) (x2= 0.2556). The effect of affinity-purified IgG phospholipid-dependent inhibitors of coagulation on the time-course of FVa generation and inactivation in normal plasma was also investigated. Anti–β2-GPI, but not antiprothrombin antibodies, hampered the inactivation of FVa by endogenous APC, thus reproducing the behavior of the original plasmas. This effect was strictly β2-GPI–dependent. In conclusion, our findings confirm that anti–β2-GPI antibodies identify patients with phospholipid-dependent inhibitors of coagulation at increased risk of thrombosis and suggest acquired APC-R as a possible explanation of the pathogenesis of the thromboembolic events.

scholarly journals Computational Studies of SARS-CoV-2 3CLpro: Insights from MD Simulations

2020 ◽  
Vol 21 (15) ◽  
pp. 5346 ◽  
Author(s):  
Alessandro Grottesi ◽  
Neva Bešker ◽  
Andrew Emerson ◽  
Candida Manelfi ◽  
Andrea R. Beccari ◽  
...  
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Health Impact ◽  
Respiratory Syndrome Virus ◽  
Enzymatic Function ◽  
Main Protease ◽  
Loop Regions ◽  
Dimeric Form ◽  
And Function ◽  
Shed Light

Given the enormous social and health impact of the pandemic triggered by severe acute respiratory syndrome 2 (SARS-CoV-2), the scientific community made a huge effort to provide an immediate response to the challenges posed by Coronavirus disease 2019 (COVID-19). One of the most important proteins of the virus is an enzyme, called 3CLpro or main protease, already identified as an important pharmacological target also in SARS and Middle East respiratory syndrome virus (MERS) viruses. This protein triggers the production of a whole series of enzymes necessary for the virus to carry out its replicating and infectious activities. Therefore, it is crucial to gain a deeper understanding of 3CLpro structure and function in order to effectively target this enzyme. All-atoms molecular dynamics (MD) simulations were performed to examine the different conformational behaviors of the monomeric and dimeric form of SARS-CoV-2 3CLpro apo structure, as revealed by microsecond time scale MD simulations. Our results also shed light on the conformational dynamics of the loop regions at the entry of the catalytic site. Studying, at atomic level, the characteristics of the active site and obtaining information on how the protein can interact with its substrates will allow the design of molecules able to block the enzymatic function crucial for the virus.

SIGN REVERSAL OF COULOM INTERACTION BETWEEN TWO QUASIPARTICLES IN MOMENTUM SPACE

2013 ◽  
Vol 27 (15) ◽  
pp. 1362035 ◽  
Author(s):  
J. D. FAN ◽  
YURIY M. MALOZOVSKY
Keyword(s):  
Interaction Energy ◽  
Common Sense ◽  
General Theorem ◽  
Fermi System ◽  
Main Concept ◽  
Sign Reversal ◽  
The Common ◽  
Definition Of ◽  
Electron Photon ◽  
Shed Light

The main misconception regarding the interaction between quasiparticles stems from the assertion that the interaction energy between two quasiparticles is exactly identical to that of the renormalized interaction between two particles due to interparticle interaction in the Fermi system. If the main concept regarding the definition of quasiparticle as a weakly excited state of the Fermi system with conservation of charge and spin is paramount (except for the charge and spin separation models), the concept of the interaction between quasiparticles is very different from the assumption in the common sense. In this paper, we will prove a general theorem that the interaction between two quasiparticles is very much different from the renormalized interaction between two particles. The major difference lies in two places: the interaction between two quasiparticles is just negative to the renormalized interaction between two particles, and the interaction energy between the two particles is proportional to the product of two Fermi liquid renormalization factors. The result shed light on the reinterpretation of Cooper's pairing without invoking electron-photon interaction.

scholarly journals Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics

2016 ◽  
Vol 113 (12) ◽  
pp. 3233-3238 ◽  
Author(s):  
Brett A. Colson ◽  
Andrew R. Thompson ◽  
L. Michel Espinoza-Fonseca ◽  
David D. Thomas
Keyword(s):  
Protein C ◽  
Binding Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Md Simulations ◽  
Cardiac Myosin ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

We have used the site-directed spectroscopies of time-resolved fluorescence resonance energy transfer (TR-FRET) and double electron–electron resonance (DEER), combined with complementary molecular dynamics (MD) simulations, to resolve the structure and dynamics of cardiac myosin-binding protein C (cMyBP-C), focusing on the N-terminal region. The results have implications for the role of this protein in myocardial contraction, with particular relevance to β-adrenergic signaling, heart failure, and hypertrophic cardiomyopathy. N-terminal cMyBP-C domains C0–C2 (C0C2) contain binding regions for potential interactions with both thick and thin filaments. Phosphorylation by PKA in the MyBP-C motif regulates these binding interactions. Our spectroscopic assays detect distances between pairs of site-directed probes on cMyBP-C. We engineered intramolecular pairs of labeling sites within cMyBP-C to measure, with high resolution, the distance and disorder in the protein’s flexible regions using TR-FRET and DEER. Phosphorylation reduced the level of molecular disorder and the distribution of C0C2 intramolecular distances became more compact, with probes flanking either the motif between C1 and C2 or the Pro/Ala-rich linker (PAL) between C0 and C1. Further insight was obtained from microsecond MD simulations, which revealed a large structural change in the disordered motif region in which phosphorylation unmasks the surface of a series of residues on a stable α-helix within the motif with high potential as a protein–protein interaction site. These experimental and computational findings elucidate structural transitions in the flexible and dynamic portions of cMyBP-C, providing previously unidentified molecular insight into the modulatory role of this protein in cardiac muscle contractility.

scholarly journals Macrochirality of Self-Assembled and Co-assembled Supramolecular Structures of a Pair of Enantiomeric Peptides

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen Guo ◽  
Yongshun Song ◽  
Yujiao Wang ◽  
Tingyuan Tan ◽  
Yuwen Ji ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Md Simulations ◽  
Supramolecular Structures ◽  
Molecular Chirality ◽  
Left Handed ◽  
Self Assembled ◽  
Shed Light ◽  
Good Agreement

Although macrochirality of peptides’ supramolecular structures has been found to play important roles in biological activities, how macrochirality is determined by the molecular chirality of the constituted amino acids is still unclear. Here, two chiral peptides, Ac-LKLHLHLQLKLLLVLFLFLALK-NH2 (KK-11) and Ac-DKDHDHDQDKDL DVDFDFDADK-NH2 (KKd-11), which were composed entirely of either L- or D-amino acids, were designed for studying the chiral characteristics of the supramolecular microstructures. It was found that monocomponent KK-11 or KKd-11 self-assembled into right- or left-handed helical nanofibrils, respectively. However, when they co-assembled with concentration ratios varied from 1:9 to 9:1, achiral nanowire-like structures were formed. Both circular dichroism and Fourier transform infrared spectra indicated that the secondary structures changed when the peptides co-assembled. MD simulations indicated that KK-11 or KKd-11 exhibited a strong propensity to self-assemble into right-handed or left-handed nanofibrils, respectively. However, when KK-11 and KKd-11 were both presented in a solution, they had a higher probability to co-assemble instead of self-sort. MD simulations indicated that, in their mixtures, they formed nanowires without handedness feature, a good agreement with experimental observation. Our results shed light on the molecular mechanisms of the macrochirality of peptide supramolecular microstructures.

scholarly journals Cellular Uptake Behaviors of Rigidity-Tunable Dendrimers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 99 ◽  
Author(s):  
Hui Liu ◽  
Jingjing Wang ◽  
Wenchao Li ◽  
Jie Hu ◽  
Min Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cellular Uptake ◽  
Biomedical Applications ◽  
Intracellular Localization ◽  
Hydrodynamic Size ◽  
Limited Information ◽  
Flow Cytometry Analysis ◽  
Core Flow ◽  
Microscopic Evaluation ◽  
Gold Nps

Understanding of the interaction between cells and nanoparticles (NPs) is critical. Despite numerous attempts to understand the effect of several parameters of NPs on their cellular uptake behaviors, such as size, shape, surface chemistry, etc., limited information is available regarding NP rigidity. Herein, we investigate the effect of rigidity on cellular uptake behaviors of NPs, using generation 5 poly(amidoamine) dendrimer as a model. By harnessing the abundant inner cavity, their rigidity could be effectively regulated by forming size-tunable gold NPs. The NPs thus formed were well characterized and displayed similar hydrodynamic size, surface potential, fluorescence intensity, and distinct rigidity (owing to differences in the size of the Au core). Flow cytometry analysis revealed a positive correlation between NP rigidity and cellular uptake of NPs. Confocal microscopic evaluation revealed that the entrapped gold NPs may affect the intracellular localization of the internalized dendrimers. The present findings can potentially guide the preparation of suitable NPs for biomedical applications.

scholarly journals Feminist Women’s Attitudes towards Feminist Men in the Canadian Atheist Movement

2020 ◽  
Vol 10 (2) ◽  
pp. 182-201
Author(s):  
Jonathan Simmons
Keyword(s):  
Research Area ◽  
Gender Inequalities ◽  
Limited Information ◽  
Structured Interviews ◽  
Gender Dynamics ◽  
Gender Egalitarianism ◽  
The One ◽  
Shed Light ◽  
Critique Of Religion

Abstract Scholars of nonreligion and atheism have become increasingly interested in how the atheist movement reproduces gender inequalities. This growing research area is especially concerned with atheist activism’s contradictory embracing of gender egalitarianism on the one hand (especially when embedded in a critique of religion) and the exclusion of women from atheist spaces. Limited information is available on male atheists who identify as feminist or who express agreement with feminist goals. Although some scholars have addressed the rejection of feminist claims within organised nonreligion, this article examines both men’s adoption of the feminist label and women’s attitudes towards feminist men in the atheist movement. Drawing from thirty-five semi-structured interviews with atheist activists in Edmonton, Alberta, Canada, I show that some feminist women perceived feminist men as passive or guided by insincere motivations (primarily to earn the attention and approval of women within atheist organisations). These findings shed light on the dilemmas of feminist men in atheist activism and contribute to understanding the gender dynamics of some atheist organisations.

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