PEP-FOLD3: faster<i>de novo</i>structure prediction for linear peptides in solution and in complex

Lamiable, Alexis; Thévenet, Pierre; Rey, Julien; Vavruša, Marek; Derreumaux, Philippe; Tufféry, Pierre

doi:10.1093/nar/gkw329

Cited by 835 publications

(692 citation statements)

References 36 publications

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“…3D structures of these peptides were modeled with the PEP-FOLD3 server61, using 200 simulation runs to sample the conformations. After PEP-FOLD3 had clustered the different conformational models, they were sorted using the sOPEP energy62 value.…”

Section: Methodsmentioning

confidence: 99%

Towards peptide vaccines against Zika virus: Immunoinformatics combined with molecular dynamics simulations to predict antigenic epitopes of Zika viral proteins

Mirza

Rafique

Ali

et al. 2016

Sci Rep

102

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The recent outbreak of Zika virus (ZIKV) infection in Brazil has developed to a global health concern due to its likely association with birth defects (primary microcephaly) and neurological complications. Consequently, there is an urgent need to develop a vaccine to prevent or a medicine to treat the infection. In this study, immunoinformatics approach was employed to predict antigenic epitopes of Zika viral proteins to aid in development of a peptide vaccine against ZIKV. Both linear and conformational B-cell epitopes as well as cytotoxic T-lymphocyte (CTL) epitopes were predicted for ZIKV Envelope (E), NS3 and NS5 proteins. We further investigated the binding interactions of altogether 15 antigenic CTL epitopes with three class I major histocompatibility complex (MHC I) proteins after docking the peptides to the binding groove of the MHC I proteins. The stability of the resulting peptide-MHC I complexes was further studied by molecular dynamics simulations. The simulation results highlight the limits of rigid-body docking methods. Some of the antigenic epitopes predicted and analyzed in this work might present a preliminary set of peptides for future vaccine development against ZIKV.

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Section: Methodsmentioning

confidence: 99%

Towards peptide vaccines against Zika virus: Immunoinformatics combined with molecular dynamics simulations to predict antigenic epitopes of Zika viral proteins

Mirza

Rafique

Ali

et al. 2016

Sci Rep

102

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“…Secondary structures were predicted using PSIPRED version 3.3 (53) and PEP-FOLD3 (54). Helical wheel diagrams were generated using HeliQuest (55).…”

Section: Cholesterol-regulated Degron Of Squalene Monooxygenase Bioinmentioning

confidence: 99%

A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis

Chua

Howe

Jatana

et al. 2017

Journal of Biological Chemistry

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Edited by Dennis R. VoelkerCholesterol biosynthesis in the endoplasmic reticulum (ER) is tightly controlled by multiple mechanisms to regulate cellular cholesterol levels. Squalene monooxygenase (SM) is the second rate-limiting enzyme in cholesterol biosynthesis and is regulated both transcriptionally and post-translationally. SM undergoes cholesterol-dependent proteasomal degradation when cholesterol is in excess. The first 100 amino acids of SM (designated SM N100) are necessary for this degradative process and represent the shortest cholesterol-regulated degron identified to date. However, the fundamental intrinsic characteristics of this degron remain unknown. In this study, we performed a series of deletions, point mutations, and domain swaps to identify a 12-residue region (residues Gln-62-Leu-73), required for SM cholesterol-mediated turnover. Molecular dynamics and circular dichroism revealed an amphipathic helix within this 12-residue region. Moreover, 70% of the variation in cholesterol regulation was dependent on the hydrophobicity of this region. Of note, the earliest known Doa10 yeast degron, Deg1, also contains an amphipathic helix and exhibits 42% amino acid similarity with SM N100. Mutating SM residues Phe-35/Ser-37/Leu-65/Ile-69 into alanine, based on the key residues in Deg1, blunted SM cholesterol-mediated turnover. Taken together, our results support a model whereby the amphipathic helix in SM N100 attaches reversibly to the ER membrane depending on cholesterol levels; with excess, the helix is ejected and unravels, exposing a hydrophobic patch, which then serves as a degradation signal. Our findings shed new light on the regulation of a key cholesterol synthesis enzyme, highlighting the conservation of critical degron features from yeast to humans.

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“…Pepfold3 server [20] prediction for the secondary structure also showed the alpha helix as the best model for all four peptides. …”

Section: Secondary Structure Characterizationmentioning

confidence: 83%

“…To achieve this, Protparam and Protscale through Expasy server [23] and the peptide calculator through Bachem page [22] were used. Secondary structure was predicted by using Pepfold3 server [20].…”

Section: Theoretical Physicochemical Propertiesmentioning

confidence: 99%

Deprotection Reagents in Fmoc Solid Phase Peptide Synthesis: Moving Away from Piperidine?

et al. 2016

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Abstract:The deprotection step is crucial in order to secure a good quality product in Fmoc solid phase peptide synthesis. 9-Fluorenylmethoxycarbonyl (Fmoc) removal is achieved by a two-step mechanism reaction favored by the use of cyclic secondary amines; however, the efficiency of the reaction could be affected by side reactions and by-product formation. Several aspects have to be taken into consideration when selecting a deprotection reagent: its physicochemical behavior, basicity (pKa) and polarity, concentration, and time of reaction, toxicity and disposability of residues and, finally, availability of reagents. This report presents a comparison of the performance of three strategies for deprotection using microwave-assisted Fmoc peptide synthesis. Four peptide sequences were synthesized using Rink amide resin with a Liberty Blue™ automated synthesizer and 4-methylpiperidine (4MP), piperidine (PP), and piperazine (PZ) as Fmoc removal reagents. In the first instance all three reagents behaved similarly. A detailed analysis showed a correlation between the hydrophobicity and size of the peptide with the yield and purity of the obtained product. The three reagents are interchangeable, and replacement of piperidine could be advantageous regarding toxicity and reagent handling.

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PEP-FOLD3: fasterde novostructure prediction for linear peptides in solution and in complex

Cited by 835 publications

References 36 publications

Towards peptide vaccines against Zika virus: Immunoinformatics combined with molecular dynamics simulations to predict antigenic epitopes of Zika viral proteins

Towards peptide vaccines against Zika virus: Immunoinformatics combined with molecular dynamics simulations to predict antigenic epitopes of Zika viral proteins

A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis

Deprotection Reagents in Fmoc Solid Phase Peptide Synthesis: Moving Away from Piperidine?

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