Prions are proteins that cause a group of invariably fatal neurodegenerative diseases, one of the most known being bovine spongiform encephalopathy. The three‐dimensional structure of PrPSc, the altered isoform of the prion protein, has not been fully elucidated yet, and studies on prion conversion mechanisms must rely on hypothetical β‐rich structures. Experimental and computational studies indicate that the use of low pH is capable to produce a gain of β‐structure content in the otherwise unstructured N‐terminal region. These in silico studies have used different PrP fragments from distinct organisms, and with different lengths and simulation protocols, making it difficult to identify the influence of the force fields on the formation of such structures. Here, we performed a systematic study of the influence of six well‐established force fields (GROMOS96 53a6, GROMOS96 43a1, AMBER99SB, AMBER99SB‐ILDN, CHARMM27, and OPLS‐AA/L) on the process of structural conversion of the Syrian hamster cellular prion protein simulated at acidic and neutral pH. From our analysis, we observe a strong dependence of the results with the different force fields employed. Additionally, only GROMOS96 53A6 and AMBER99SB force fields are capable to capture a high β‐sheet formation at acidic pH and adequately reproduce the neutral pH. In both cases, the β‐sheet elongation seems to be guided by the movement of the N‐terminal tail toward the N‐terminal of α‐helix HB under acidic condition. These results comprise the most wide‐ranging study to date correlating force fields to structural changes in the cellular prion protein. © 2018 Wiley Periodicals, Inc.
Plant RNases T2 are involved in several physiological and developmental processes, including inorganic phosphate starvation, senescence, wounding, defense against pathogens, and the self-incompatibility system. Solanaceae RNases form three main clades, one composed exclusively of S-RNases and two that include S-like RNases. We identified several positively selected amino acids located in highly flexible regions of these molecules, mainly close to the B1 and B2 substrate-binding sites in S-like RNases and the hypervariable regions of S-RNases. These differences between S- and S-like RNases in the flexibility of amino acids in substrate-binding regions are essential to understand the RNA-binding process. For example, in the S-like RNase NT, two positively selected amino acid residues (Tyr156 and Asn134) are located at the most flexible sites on the molecular surface. RNase NT is induced in response to tobacco mosaic virus infection; these sites may thus be regions of interaction with pathogen proteins or viral RNA. Differential selective pressures acting on plant ribonucleases have increased amino acid variability and, consequently, structural differences within and among S-like RNases and S-RNases that seem to be essential for these proteins play different functions.
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