scholarly journals Prediction of LncRNA-encoded small peptides in glioma and oligomer channel functional analysis using in silico approaches

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248634
Author(s):  
Yipeng Cao ◽  
Rui Yang ◽  
Imshik Lee ◽  
Wenwen Zhang ◽  
Jiana Sun ◽  
...  
Keyword(s):  
Water Channel ◽  
Free Energy Calculations ◽  
Open Reading Frames ◽  
Small Peptides ◽  
Ion Regulation ◽  
Transmembrane Peptides ◽  
Theoretical Support ◽  
Dynamics Simulations ◽  
Functional Mechanisms ◽  
Small Open Reading Frames

Glioma is a lethal malignant brain cancer, and many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating tumor proliferation, migration, apoptosis, and differentiation. Recently, new studies have suggested that some long noncoding RNAs containing small open reading frames can encode small peptides and form oligomers for water or ion regulation. However, because the peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatics methods to identify and evaluate lncRNAs, which may encode small transmembrane peptides in gliomas. Combining ab initio homology modeling, molecular dynamics simulations, and free energy calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs. We found that one key hub lncRNA, namely, DLEU1, which contains two smORFs (ORF1 and ORF8), encodes small peptides that form pentameric channels. The mechanics of water and ion (Na+ and Cl-) transport through this pentameric channel were simulated. The potential mean force of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 permeated neither ions nor water. This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, this study provides a theoretical basis for drug development.

scholarly journals Prediction of LncRNA Encoded Small Peptides in Glioma and The Oligomer Channel Functional Analysis Using in Silico Approaches

2020 ◽  
Author(s):  
Yipeng Cao ◽  
Rui Yang ◽  
Imshik Lee ◽  
Wenwen Zhang ◽  
Jiana Sun ◽  
...  
Keyword(s):  
Water Channel ◽  
Potential Of Mean Force ◽  
Open Reading Frames ◽  
Small Peptides ◽  
Ion Regulation ◽  
Transmembrane Peptides ◽  
Theoretical Support ◽  
Dynamics Simulations ◽  
Functional Mechanisms ◽  
Small Open Reading Frames

AbstractGlioma is lethal malignant brain cancers, many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating glioma proliferation, migration, apoptosis and differentiation. Recently, new studies have suggested that some long noncoding RNAs (lncRNAs) containing small open reading frames (smORFs), can encode small peptides and form oligomers for water or ion regulation. However, because these peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatic methods and softwares to identify and evaluate lncRNAs in gliomas that may encode small transmembrane peptides. Combining ab initio homology modeling, molecular dynamics simulations and energetic calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs.We found that one key hub lncRNA, DLEU1, which contains two smORFs (ORF1 and ORF8) could encode small peptides that form pentameric channels. The mechanics of water and ion (Na + and Cl-) transport through this pentameric channel were simulated. The potential of mean force (PMF) of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 neither permeating ions nor water.This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, it provides a theoretical basis for drug development.

scholarly journals FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs

2020 ◽  
Vol 6 (4) ◽  
pp. 41
Author(s):  
Mihnea P. Dragomir ◽  
Ganiraju C. Manyam ◽  
Leonie Florence Ott ◽  
Léa Berland ◽  
Erik Knutsen ◽  
...  
Keyword(s):  
Open Reading Frames ◽  
Start Codon ◽  
Small Peptides ◽  
Reading Frame ◽  
Cellular Processes ◽  
New Class ◽  
Web Resource ◽  
Non Coding Rnas ◽  
Functional Peptides ◽  
Small Open Reading Frames

Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading frames (smORFs), many initiating with the traditional AUG start codon but terminating with atypical stop codons, suggesting a different biogenesis. The ncRNA-encoded peptides (ncPEPs) are gradually becoming appreciated as a new class of functional molecules that contribute to diverse cellular processes, and are deregulated in different diseases contributing to pathogenesis. As multiple publications have identified unique ncPEPs, we appreciated the need for assembling a new web resource that could gather information about these functional ncPEPs. We developed FuncPEP, a new database of functional ncRNA encoded peptides, containing all experimentally validated and functionally characterized ncPEPs. Currently, FuncPEP includes a comprehensive annotation of 112 functional ncPEPs and specific details regarding the ncRNA transcripts that encode these peptides. We believe that FuncPEP will serve as a platform for further deciphering the biologic significance and medical use of ncPEPs. The link for FuncPEP database can be found at the end of the Introduction Section.

Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames

Science ◽  
2013 ◽  
Vol 341 (6150) ◽  
pp. 1116-1120 ◽  
Author(s):  
Emile G. Magny ◽  
Jose Ignacio Pueyo ◽  
Frances M.G. Pearl ◽  
Miguel Angel Cespedes ◽  
Jeremy E. Niven ◽  
...  
Keyword(s):  
Amino Acids ◽  
Muscle Contraction ◽  
Dna Sequences ◽  
Calcium Transport ◽  
Calcium Uptake ◽  
Open Reading Frames ◽  
Insect Development ◽  
Small Peptides ◽  
Reading Frames ◽  
Small Open Reading Frames

Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.

scholarly journals Extensive translation of small Open Reading Frames revealed by Poly-Ribo-Seq

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Julie L Aspden ◽  
Ying Chen Eyre-Walker ◽  
Rose J Phillips ◽  
Unum Amin ◽  
Muhammad Ali S Mumtaz ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Open Reading Frames ◽  
Small Peptides ◽  
Functional Roles ◽  
Genome Wide ◽  
A Genome ◽  
Non Coding Rnas ◽  
Reading Frames ◽  
Small Open Reading Frames

Thousands of small Open Reading Frames (smORFs) with the potential to encode small peptides of fewer than 100 amino acids exist in our genomes. However, the number of smORFs actually translated, and their molecular and functional roles are still unclear. In this study, we present a genome-wide assessment of smORF translation by ribosomal profiling of polysomal fractions in Drosophila. We detect two types of smORFs bound by multiple ribosomes and thus undergoing productive translation. The ‘longer’ smORFs of around 80 amino acids resemble canonical proteins in translational metrics and conservation, and display a propensity to contain transmembrane motifs. The ‘dwarf’ smORFs are in general shorter (around 20 amino-acid long), are mostly found in 5′-UTRs and non-coding RNAs, are less well conserved, and have no bioinformatic indicators of peptide function. Our findings indicate that thousands of smORFs are translated in metazoan genomes, reinforcing the idea that smORFs are an abundant and fundamental genome component.

Aggregation of small peptides studied by molecular dynamics simulations

2006 ◽  
Vol 65 (4) ◽  
pp. 914-921 ◽  
Author(s):  
Dagmar Flöck ◽  
Giulia Rossetti ◽  
Isabella Daidone ◽  
Andrea Amadei ◽  
Alfredo Di Nola
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Small Peptides ◽  
Dynamics Simulations

scholarly journals Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Alejandro Gil L. ◽  
Pedro A. Valiente ◽  
Pedro G. Pascutti ◽  
Tirso Pons
Keyword(s):  
Structure Function ◽  
Free Energy Calculations ◽  
Special Focus ◽  
Binding Modes ◽  
Linear Interaction ◽  
Lead Compounds ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Dynamics Simulations ◽  
Selection Of

The development of efficient and selective antimalariais remains a challenge for the pharmaceutical industry. The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs. Combinatorial synthesis is currently being used to generate inhibitor libraries for these enzymes, and together with computational methodologies have been demonstrated capable for the selection of lead compounds. The high structural flexibility of plasmepsins, revealed by their X-ray structures and molecular dynamics simulations, made even more complicated the prediction of putative binding modes, and therefore, the use of common computational tools, like docking and free-energy calculations. In this review, we revised the computational strategies utilized so far, for the structure-function relationship studies concerning the plasmepsin family, with special focus on the recent advances in the improvement of the linear interaction estimation (LIE) method, which is one of the most successful methodologies in the evaluation of plasmepsin-inhibitor binding affinity.

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