scholarly journals The Amino Acid Composition of Quadruplex Binding Proteins Reveals a Shared Motif and Predicts New Potential Quadruplex Interactors

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2341 ◽  
Author(s):  
Václav Brázda ◽  
Jiří Červeň ◽  
Martin Bartas ◽  
Nikol Mikysková ◽  
Jan Coufal ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Binding Proteins ◽  
Homo Sapiens ◽  
Specific Protein ◽  
Nucleic Acid Binding ◽  
Dna Structures ◽  
G Quadruplex ◽  
Arginine Residues

The importance of local DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, G-quadruplexes are perhaps the most well-characterized to date, and their presence has been demonstrated in many genomes, including that of humans. G-quadruplexes are selectively bound by many regulatory proteins. In this paper, we have analyzed the amino acid composition of all seventy-seven described G-quadruplex binding proteins of Homo sapiens. Our comparison with amino acid frequencies in all human proteins and specific protein subsets (e.g., all nucleic acid binding) revealed unique features of quadruplex binding proteins, with prominent enrichment for glycine (G) and arginine (R). Cluster analysis with bootstrap resampling shows similarities and differences in amino acid composition of particular quadruplex binding proteins. Interestingly, we found that all characterized G-quadruplex binding proteins share a 20 amino acid long motif/domain (RGRGR GRGGG SGGSG GRGRG) which is similar to the previously described RG-rich domain (RRGDG RRRGG GGRGQ GGRGR GGGFKG) of the FRM1 G-quadruplex binding protein. Based on this protein fingerprint, we have predicted a new set of potential G-quadruplex binding proteins sharing this interesting domain rich in glycine and arginine residues.

scholarly journals Amino Acid Composition in Various Types of Nucleic Acid-Binding Proteins

2021 ◽  
Vol 22 (2) ◽  
pp. 922
Author(s):  
Martin Bartas ◽  
Jiří Červeň ◽  
Simona Guziurová ◽  
Kristyna Slychko ◽  
Petr Pečinka
Keyword(s):  
Amino Acid ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Binding Proteins ◽  
Current Knowledge ◽  
Special Focus ◽  
Nucleic Acid Binding ◽  
Nucleic Acid Binding Proteins

Nucleic acid-binding proteins are traditionally divided into two categories: With the ability to bind DNA or RNA. In the light of new knowledge, such categorizing should be overcome because a large proportion of proteins can bind both DNA and RNA. Another even more important features of nucleic acid-binding proteins are so-called sequence or structure specificities. Proteins able to bind nucleic acids in a sequence-specific manner usually contain one or more of the well-defined structural motifs (zinc-fingers, leucine zipper, helix-turn-helix, or helix-loop-helix). In contrast, many proteins do not recognize nucleic acid sequence but rather local DNA or RNA structures (G-quadruplexes, i-motifs, triplexes, cruciforms, left-handed DNA/RNA form, and others). Finally, there are also proteins recognizing both sequence and local structural properties of nucleic acids (e.g., famous tumor suppressor p53). In this mini-review, we aim to summarize current knowledge about the amino acid composition of various types of nucleic acid-binding proteins with a special focus on significant enrichment and/or depletion in each category.

scholarly journals WRAP-based nanoparticles for siRNA delivery: a SAR study and a comparison with lipid-based transfection reagents

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Karidia Konate ◽  
Emilie Josse ◽  
Milana Tasic ◽  
Karima Redjatti ◽  
Gudrun Aldrian ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gene Silencing ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Sirna Delivery ◽  
Cell Penetrating Peptides ◽  
Sirna Transfection ◽  
Arginine Residues ◽  
Sar Study

AbstractRecently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells. In order to gain more information about the relationship between amino acid composition, nanoparticle formation and cellular internalization of these peptides composed of only three amino acids (leucine, arginine and tryptophan), we performed a structure–activity relationship (SAR) study. First, we compared our WRAP1 and WRAP5 peptides with the C6M1 peptide also composed of the same three amino acids and showing similar behaviors in siRNA transfection. Afterwards, to further define the main determinants in the WRAP activity, we synthesized 13 new WRAP analogues harboring different modifications like the number and location of leucine and arginine residues, the relative location of tryptophan residues, as well as the role of the α-helix formation upon proline insertions within the native WRAP sequence. After having compared the ability of these peptides to form peptide-based nanoparticles (PBNs) using different biophysical methods and to induce a targeted gene silencing in cells, we established the main sequential requirements of the amino acid composition of the WRAP peptide. In addition, upon measuring the WRAP-based siRNA transfection ability into cells compared to several non-peptide transfection agents available on the markets, we confirmed that WRAP peptides induced an equivalent level of targeted gene silencing but in most of the cases with lower cell toxicity as clearly shown in clonogenic assays.

Identify DNA-Binding Proteins with Optimal Chou’s Amino Acid Composition

2012 ◽  
Vol 19 (4) ◽  
pp. 398-405 ◽  
Author(s):  
Xiao-Wei Zhao ◽  
Xiang-Tao Li ◽  
Zhi-Qiang Ma ◽  
Ming-Hao Yin
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Binding Proteins ◽  
Dna Binding Proteins

Identification of Distinct Amino Acid Composition of Human Cruciform Binding Proteins

2019 ◽  
Vol 53 (1) ◽  
pp. 97-106 ◽  
Author(s):  
M. Bartas ◽  
P. Bažantová ◽  
V. Brázda ◽  
J. C. Liao ◽  
J. Červeň ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Binding Proteins

scholarly journals Pathway-Specific Protein Domains (PSPD) Discrimination by Using a Hybrid Feature Space Based on Deep Neural Network(DNN)

2020 ◽  
Author(s):  
Ali Ghulam ◽  
XiuJuan Lei ◽  
Yuchen Zhang ◽  
Zhenqiang Wu
Keyword(s):  
Neural Network ◽  
Machine Learning ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Correlation Coefficient ◽  
Acid Composition ◽  
Deep Neural Network ◽  
Protein Domains ◽  
Specific Protein ◽  
Matthew’S Correlation Coefficient

Abstract The Pathway-specific protein domains (PSPDs) are important tools in examining drug growth as they provide a fast, reliable, and inexpensive way of estimating complex new molecular targets in specific diseases. The protein architecture prevents the formation of a direct correlation between signal transduction behavior and cellular structure. Accordingly, protein–tissue factor pathway inhibitor 2 isotypes 1 precursors have been used to encode peptide sequence information into specific feature structures. The measurable structure-activity classification model obtained by machine learning technology can predict pathway-specific protein interactions and new signaling peptides. We introduce deep neural network (DNN)-based PSPDs, abbreviated as DNNPSPDs, as the first pathway-specific protein domain that is built based on five extant models, namely, the AAindex, pseudo-amino acid composition, amino acid composition, composition mood of pseudoamino acids, and dipeptide composition. A total of 900 proteins with undetermined roles collected from the PDB data base are tested to evaluate the predictive power of this model. Various combinations of the available feature selection technologies are also combined to process a hybrid function space. DNNPSPDs predicts PSPDs by using features that are automatically learned from primary protein sequences. The sequences of pathway-associated proteins are sequentially fed into and decoded in neural network layers. Several classifications are also employed. DNNPSPDs achieves a prediction accuracy of 0.957 at a Matthew’s correlation coefficient (MCC) of 91.86%, with DPC, and 2nd achieve high prediction score 0.936 at Matthew’s correlation coefficient (MCC) of 88.02%, accuracy which is probably better. In terms of ROC–AUC, DNNPSPDs achieves a ROC–AUC curve of 0.982, which is larger than that of the other machine learning classifiers. A study using an alternative dataset reveals that our primary pathways, as pathway-specific protein domains, have accurate and reliable associations, thereby proving the viability of the proposed DNNPSPDs.

scholarly journals WRAP-based nanoparticles for siRNA delivery: A SAR study and a comparison with lipid-based transfection reagents.

2020 ◽  
Author(s):  
Karidia Konate ◽  
Emilie Josse ◽  
Milana Tasic ◽  
Karima Redjatti ◽  
Gudrun Aldrian ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gene Silencing ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Cell Penetrating Peptides ◽  
Luciferase Assay ◽  
Sirna Transfection ◽  
Arginine Residues ◽  
Sar Study

Abstract Recently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells. In order to gain more information about the relationship between amino acid composition, nanoparticle formation and cellular internalization of these peptides composed of only three amino acids (leucine, arginine and tryptophan), we perform a structure activity relationship (SAR) study. First, we compared our WRAP1 and WRAP5 peptides with the C6M1 peptide also composed of the same three amino acids and showing similar behaviors in siRNA transfection. Afterwards, to further define the main determinants in the WRAP activity, we synthesized 13 new WRAP analogues harboring different modifications like the number and location of leucine and arginine residues, the relative location of tryptophan residues, as well as the role of the α-helix formation upon proline insertions within the native WRAP sequence. After having compare the ability of these peptides to form peptide-based nanoparticles (PBNs) or not using different biophysical methods (circular dichroism, dynamic light scattering, gel shift assay) and to induce a targeted gene silencing (luciferase assay) in cells, we were able to establish the main sequential requirements of the amino acid composition of the WRAP peptides to maintain a good siRNA transfection efficacy. In addition, upon measuring the WRAP-based siRNA transfection ability into cells compared to several non-peptide transfection agents available on the markets, we confirmed that WRAP peptides induced an equivalent level of targeted gene silencing but in most of the cases with significant lower cell toxicity as clearly shown in clonogenic assays.

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