Navegando por Palavras-chave "molecular dynamics"
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- ItemSomente MetadadadosEvidences for the action mechanism of angiotensin II and its analogs on Plasmodium sporozoite membranes(Wiley, 2016) Torossian Torres, Marcelo Der; Silva, Adriana Farias; Alves, Flavio Lopes [UNIFESP]; Capurro, Margareth Lara; Miranda, Antonio [UNIFESP]; Cordeiro, Rodrigo Maghdissian; Oliveira Junior, Vani XavierMalaria is an infectious disease responsible for approximately one million deaths annually. Oligopeptides such as angiotensin II (AII) and its analogs are known to have antimalarial effects against Plasmodium gallinaceum and Plasmodium falciparum. However, their mechanism of action is still not fully understood at the molecular level. In the work reported here, we investigated this issue by comparing the antimalarial activity of AII with that of (i) its diastereomer formed by only d-amino acids; (ii) its isomer with reversed sequence; and (iii) its analogs restricted by lactam bridges, the so-called VC5 peptides. Data from fluorescence spectroscopy indicated that the antiplasmodial activities of both all-D-AII and all-D-VC5 were as high as those of the related peptides AII and VC5, respectively. In contrast, retro-AII had no significant effect against P. gallinaceum. Conformational analysis by circular dichroism suggested that AII and its active analogs usually adopted a -turn conformation in different solutions. In the presence of membrane-mimetic micelles, AII had also a -turn conformation, while retro-AII was random. Molecular dynamics simulations demonstrated that the AII chains were slightly more bent than retro-AII at the surface of a model membrane. At the hydrophobic membrane interior, however, the retro-AII chain was severely coiled and rigid. AII was much more flexible and able to experience both straight and coiled conformations. We took it as an indication of the stronger ability of AII to interact with membrane headgroups and promote pore formation. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd.
- ItemAcesso aberto (Open Access)Graphene/Ionic Liquid Ultracapacitors: Does Ionic Size Correlate with Storage Energy Performance?(RSC, 2018-04-21) Chaban, Vitaly V.; Andreeva, Nadezha A.; Eudes, Fileti [UNIFESP]; http://lattes.cnpq.br/5294929829300325An electric double layer ultracapacitor stores energy in an electric double layer formed near its electrolyte/electrode interfaces. Graphene-based ultracapacitors, because of their outstanding performance, have attracted significant research interest. Optimization of ultracapacitor performance requires understanding the correlation of molecular characteristic of the device (such as structure, inter-ionic and ion-electrode interactions) with its macroscopic properties. Herein, we report molecular dynamics study of how an ionic volume impacts a double-layer capacitance. Four systems were probed: large cation + large anion, large cation + small anion, small cation + large anion, small cation + small anion. Our results show that the structuring of the ionic liquid is driven by the electrolyte-electrode interactions in the ultracapacitor, which are predominantly of the van der Waals type. Storage density energies are similar for all ultracapacitors, being in the range of 24 to 28 J cm-3 at 5.0V. Our results present a comparative analysis of the performances of four different ILs confined between two graphene electrodes. Although the best performance has been observed for the IL with ions (cations and anions) of equal sizes, no definite conclusion about the correlation of the performance to the ionic size ratio can be made from the present study.
- ItemSomente MetadadadosIsomannide-Based Peptidomimetics as Inhibitors for Human Tissue Kallikreins 5 and 7(Amer Chemical Soc, 2014-02-01) Oliveira, Jocelia P. C.; Freitas, Renato F.; Melo, Leandro Silva de; Barros, Thalita G.; Santos, Jorge A. N.; Juliano, Maria A. [UNIFESP]; Pinheiro, Sergio; Blaber, Michael; Juliano, Luiz [UNIFESP]; Muri, Estela M. F.; Puzer, Luciano; Universidade Federal do ABC (UFABC); Johns Hopkins Univ; Universidade Federal Fluminense (UFF); Inst Fed Educ Ciencia & Tecnol Sul Minas Gerais; Universidade Federal de São Paulo (UNIFESP); Florida State UnivHuman kallikrein 5 (KLK5) and 7 (KLK7) are potential targets for the treatment of skin inflammation and cancer. Previously, we identified isomannide derivatives as potent and competitive KLK7 inhibitors. the introduction of N-protected amino acids into the isomannide-based scaffold was studied. Some KLK5 inhibitors with submicromolar affinity (K-i values of 0.3-0.7 mu M) were identified, and they were 6- to 13-fold more potent than our previous hits. Enzyme kinetics studies and the determination of the mechanism of inhibition confirmed that the new isomannide-based derivatives are competitive inhibitors of both KLK5 and KLK7. Molecular docking and MD simulations of selected inhibitors into the KLK5 binding site provide insight into the molecular mechanism by which these compounds interact with the enzyme. the promising results obtained in this study open new prospects on the design and synthesis of highly specific KLK5 and KLK7 inhibitors.
- ItemSomente MetadadadosMolecular dynamics and circular dichroism studies of human and rat C-peptides(Elsevier B.V., 2006-12-01) Mares-Guia, Thiago Renno; Maigret, Bernard; Martins, Natalia Florencio; Turchetti Maia, Ana Luiza; Vilela, Luciano; Inacio Ramos, Carlos Henrique; Neto, Luiz Juliano; Juliano, Maria Aparecida; Mares-Guia, Marcos Luiz dos; Santoro, Marcelo Matos; Universidade Federal de Minas Gerais (UFMG); Henri Poincare Univ; Universidade de Brasília (UnB); Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA); Biomm SA; Lab Nacl Luz Sincrotron; Universidade Federal de São Paulo (UNIFESP)Proinsulin C-peptide has been recently described as an endogenous peptide hormone, responsible for important physiological functions others than its role in proinsulin processing. Accumulating evidences that C-peptide exerts beneficial effects in the treatment of long term complications of patients with type I diabetes mellitus indicate that this molecule may be administered together with insulin in future therapies. Despite its clear pharmacological interest, the secondary and three-dimensional (3D) structures of human C-peptide are still points of controversy. in the present work we report molecular dynamics (MD) simulations of human, rat I and rat II C-peptides. A common experimental strategy applied to all peptides consisted of homology building followed by multinanosecond MD simulations in vacuum and water. Circular dichroism (CD) experiments of each peptide in the absence and presence of 2,2,2-trifluoroethanol (TFE) were performed to support validation of the theoretical models. A multiple sequence alignment of 23 known mammalian C-peptides was constructed to identify significant conserved sites that would be important for the maintenance of secondary and tertiary structures. the analysis of the molecular dynamics trajectories for the human, rat I and rat II molecules have shown quite different general behavior, being the human C-peptide more flexible than the two others. Human and rat C-peptides exhibit very stable turn-like structures at the middle and C-terminal regions, which have been described as potential active sites of C-peptides. Human C-peptide also presented a short alpha-helix throughout the MD, which was not found in the rat molecules. CD data is in very good agreement with the MD results and both methods were able to identify a greater structural stability and potential in rat C-peptides when compared to the human C-peptide. the simulation results are discussed and validated in the light of multiple sequence alignment, recent experimental data from the literature and our own CD experiments. (c) 2006 Published by Elsevier Inc.