Biology subjects

Silva, S.

Publications and source records attributed to Silva, S..

2 recordsLinked to original sources

bioRxiv2018

The SIRAH force field 2.0: Altius, Fortius, Citius

A new version of the coarse-grained (CG) SIRAH force field for proteins has been developed. Modifications to bonded and non-bonded interactions on the existing molecular topologies significantly ameliorate the structural description and flexibility of a non-redundant set of proteins. The SIRAH 2.0 force field has also been ported to the popular simulation package AMBER, which along with the former implementation in GROMACS expands significantly the potential range of users and performance of this CG force field on CPU/GPU codes.\n\nAs a non-trivial example of application, we undertook the structural and dynamical analysis of the most abundant and conserved calcium-binding protein, namely, Calmodulin (CaM). CaM is constituted by two calcium-binding motifs called EF-hands, which in presence of Calcium specifically recognize a cognate peptide by embracing it. CG simulations of CaM bound to four Calcium ions in the presence or absence of a binding peptide (holo and apo forms, respectively), resulted in good and stable ion coordination. The simulation of the holo form starting from an experimental structure sampled near-native conformations, retrieving quasi-atomistic precision. Removing the binding peptide enabled the EF-hands to perform large reciprocal movements, comparable to those observed in NMR structures. On the other hand, the isolated peptide starting from the helical conformation experienced spontaneous unfolding, in agreement with previous experimental data. However, repositioning the peptide in the neighborhood of one EF-hand not only prevented the peptide unfolding but also drove CaM to a fully bound conformation with both EF-hands embracing the cognate peptide, resembling the experimental holo structure.\n\nTherefore, SIRAH 2.0 showed the capacity to handle a number of structurally and dynamically challenging situations including metal ion coordination, unbiased conformational sampling, and specific protein-peptide recognition.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC=\"FIGDIR/small/436774_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@1d1ecc3org.highwire.dtl.DTLVardef@10f1a04org.highwire.dtl.DTLVardef@752a49org.highwire.dtl.DTLVardef@2b5746_HPS_FORMAT_FIGEXP M_FIG TOC. C_FIG

biophysics↗

bioRxiv2017

Plasmodium simium causing human malaria: a zoonosis with outbreak potential in the Rio de Janeiro Brazilian Atlantic forest

BackgroundMalaria was eliminated from Southern and Southeastern Brazil over 50 years ago. However, an increasing number of autochthonous episodes attributed to Plasmodium vivax have been recently reported in the Atlantic forest region of Rio de Janeiro State. As P. vivax-like non-human primate malaria parasite species Plasmodium simium is locally enzootic, we performed a molecular epidemiological investigation in order to determine whether zoonotic malaria transmission is occurring.\n\nMethodsBlood samples of humans presenting signs and/or symptoms suggestive of malaria as well as from local howler-monkeys were examined by microscopy and PCR. Additionally, a molecular assay based on sequencing of the parasite mitochondrial genome was developed to distinguish between P. vivax and P. simium, and applied to 33 cases from outbreaks occurred in 2015 and 2016.\n\nResultsOf 28 samples for which the assay was successfully performed, all were shown to be P. simium, indicating the zoonotic transmission of this species to humans in this region. Sequencing of the whole mitochondrial genome of three of these cases showed that P. simium is most closely related to P. vivax parasites from South American.\n\nFindingsThe explored malaria outbreaks were caused by P. simium, previously considered a monkey-specific malaria parasite, related to but distinct from P. vivax, and which has never conclusively been shown to infect humans before.\n\nInterpretationThis unequivocal demonstration of zoonotic transmission, 50 years after the only previous report of P. simium in man, leads to the possibility that this parasite has always infected humans in this region, but that it has been consistently misdiagnosed as P. vivax due to a lack of molecular typing techniques. Thorough screening of the local non-human primate and anophelines is required to evaluate the extent of this newly recognized zoonotic threat to public health and malaria eradication in Brazil.\n\nFundingFundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado de Rio de Janeiro (Faperj), The Brazilian National Council for Scientific and Technological Development (CNPq), JSPS Grant-in-Aid for scientific research, Secretary for Health Surveillance (SVS) of the Ministry of Health, Global Fund, and PRONEX Program of the CNPq.

genetics↗