scholarly journals DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase

2017 ◽  
Vol 50 ◽  
Author(s):  
Amirhossein Taghavi ◽  
Paul van der Schoot ◽  
Joshua T. Berryman
Keyword(s):  
Amino Acids ◽  
Double Helix ◽  
Phase 1 ◽  
Weak Form ◽  
Organic Salt ◽  
Atomistic Calculations ◽  
Function Relationship ◽  
The Stability ◽  
World Hypothesis ◽  
Alignment Errors

AbstractUsing atomistic simulations, we show the formation of stable triplet structure when particular GC-rich DNA duplexes are extended in solution over a timescale of hundreds of nanoseconds, in the presence of organic salt. We present planar-stacked triplet disproportionated DNA (Σ DNA) as a possible solution phase of the double helix under tension, subject to sequence and the presence of stabilising co-factors. Considering the partitioning of the duplexes into triplets of base pairs as the first step of operation of recombinase enzymes like RecA, we emphasise the structure–function relationship in Σ DNA. We supplement atomistic calculations with thermodynamic arguments to show that codons for ‘phase 1’ amino acids (those appearing early in evolution) are more likely than a lower entropy GC-rich sequence to form triplets under tension. We further observe that the four amino acids supposed (in the ‘GADV world’ hypothesis) to constitute the minimal set to produce functional globular proteins have the strongest triplet-forming propensity within the phase 1 set, showing a series of decreasing triplet propensity with evolutionary newness. The weak form of our observation provides a physical mechanism to minimise read frame and recombination alignment errors in the early evolution of the genetic code.

scholarly journals Molecular basis of Arginine and Lysine DNA sequence-dependent thermo-stability modulation

2022 ◽  
Vol 18 (1) ◽  
pp. e1009749
Author(s):  
Benjamin Martin ◽  
Pablo D. Dans ◽  
Milosz Wieczór ◽  
Nuria Villegas ◽  
Isabelle Brun-Heath ◽  
...  
Keyword(s):  
Amino Acids ◽  
Double Helix ◽  
Dna Oligomers ◽  
Organic Ions ◽  
Sequence Dependent ◽  
Structure Flexibility ◽  
The Difference ◽  
The Stability ◽  
Thermo Stability

We have used a variety of theoretical and experimental techniques to study the role of four basic amino acids–Arginine, Lysine, Ornithine and L-2,4-Diaminobutyric acid–on the structure, flexibility and sequence-dependent stability of DNA. We found that the presence of organic ions stabilizes the duplexes and significantly reduces the difference in stability between AT- and GC-rich duplexes with respect to the control conditions. This suggests that these amino acids, ingredients of the primordial soup during abiogenesis, could have helped to equalize the stability of AT- and GC-rich DNA oligomers, facilitating a general non-catalysed self-replication of DNA. Experiments and simulations demonstrate that organic ions have an effect that goes beyond the general electrostatic screening, involving specific interactions along the grooves of the double helix. We conclude that organic ions, largely ignored in the DNA world, should be reconsidered as crucial structural elements far from mimics of small inorganic cations.

scholarly journals COPIGMENTAÇÃO INTRA E INTERMOLECULAR DE ANTOCIANINAS: UMA REVISÃO

2003 ◽  
Vol 21 (2) ◽  
Author(s):  
LEILA D. FALCÃO ◽  
DENISE M. BARROS ◽  
CONY GAUCHE ◽  
MARILDE T. BORDIGNON LUIZ
Keyword(s):  
Amino Acids ◽  
Literature Review ◽  
The Stability

Este trabalho apresenta revisão de literatura sobre a reação de copigmentação intra e intermolecular e sua relevância na estabilização de antocianinas. Flavonóides não-antociânicos, alcalóides, aminoácidos e nucleosídios, entre outros, podem atuar como copigmentos de antocianinas. O aumento na estabilidade das antocianinas ocorre devido à proteção fornecida pelo copigmento frente à reação de hidratação do cátion flavilium. Estudos ainda são necessários para avaliar a estabilidade de antocianinas adicionadas de copigmentos em sistemas modelos de alimentos, visando aumentar o espectro de aplicação dessas como corantes em alimentos e bebidas. ANTHOCYANINS INTRA AND INTERMOLECULAR COPIGMENTATION: A REVIEW Abstract This research presents literature review about the reaction of intra and intermolecular copigmentation and its revealance in anthocyanins stabilization. Non-anthocyanic flavonoids, alkaloids, amino acids, nucleosides, and others, can act as anthocyanins copigments. The increase in the stability of anthocyanins occurs due to protection supplied by the copigment towards the hydratation reaction of colored flavylium cation. Studies to evaluate anthocyanins stabilization added of copigments in food models system are still necessary, aiming to enhance the application spectra as colorants in foods and beverages.

scholarly journals H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.

1995 ◽  
Vol 181 (5) ◽  
pp. 1817-1825 ◽  
Author(s):  
J M Vyas ◽  
J R Rodgers ◽  
R R Rich
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Temperature Shift ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Compensatory Adaptation ◽  
Chemotactic Peptides ◽  
The Stability ◽  
Formyl Peptides

The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N-formylated peptides to cytotoxic T lymphocytes. This requirement potentially places severe constraints on the number of peptides that M3a can present to the immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is expressed at very low levels on the cell surface, but can be induced significantly by the addition of specific peptides at 27 degrees C. Using this assay, we show that M3a binds many very short N-formyl peptides, including N-formyl chemotactic peptides and canonical octapeptides. This observation is in sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids binding to most class I-a molecules and the class I-b molecule Qa-2. Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as low as 100 nM. While N-formyl peptides as short as two amino acids in length stabilized expression of M3a-Ld, increasing the length of these peptides added to the stability of peptide-MHC complexes as determined by 27-37 degrees C temperature shift experiments. We propose that relaxation of the length rule may represent a compensatory adaptation to maximize the number of peptides that can be presented by H-2M3a.

scholarly journals Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism

2018 ◽  
Vol 19 (11) ◽  
pp. 3524 ◽  
Author(s):  
Guodong Hu ◽  
Xiu Yu ◽  
Yunqiang Bian ◽  
Zanxia Cao ◽  
Shicai Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Noncoding Rna ◽  
Md Simulations ◽  
Normal Function ◽  
Toxin Complex ◽  
Potentials Of Mean Force ◽  
Protein Toxins ◽  
Function Relationship ◽  
The Stability ◽  
Smd Simulations

ToxIN is a triangular structure formed by three protein toxins (ToxNs) and three specific noncoding RNA antitoxins (ToxIs). To respond to stimuli, ToxI is preferentially degraded, releasing the ToxN. Thus, the dynamic character is essential in the normal function interactions between ToxN and ToxI. Here, equilibrated molecular dynamics (MD) simulations were performed to study the stability of ToxN and ToxI. The results indicate that ToxI adjusts the conformation of 3′ and 5′ termini to bind to ToxN. Steered molecular dynamics (SMD) simulations combined with the recently developed thermodynamic integration in 3nD (TI3nD) method were carried out to investigate ToxN unbinding from the ToxIN complex. The potentials of mean force (PMFs) and atomistic pictures suggest the unbinding mechanism as follows: (1) dissociation of the 5′ terminus from ToxN, (2) missing the interactions involved in the 3′ terminus of ToxI without three nucleotides (G31, A32, and A33), (3) starting to unfold for ToxI, (4) leaving the binding package of ToxN for three nucleotides of ToxI, (5) unfolding of ToxI. This work provides information on the structure-function relationship at the atomistic level, which is helpful for designing new potent antibacterial drugs in the future.

scholarly journals Thermal stability of amino acids in meals and feeds used in shrimp farming

Gaia Scientia ◽  
2016 ◽  
Vol 10 (4) ◽  
pp. 372-389
Author(s):  
João Paulo de Sousa Prado ◽  
José Marcelino Oliveira Cavalheiro ◽  
Thiago Brandão Cavalheiro ◽  
Fernanda Vanessa Gomes da Silva
Keyword(s):  
Amino Acids ◽  
Elevated Temperatures ◽  
Amino Acid Content ◽  
Storage Conditions ◽  
Shrimp Farming ◽  
Protein Levels ◽  
Commercial Feed ◽  
The Stability ◽  
The Right ◽  
And Control

The Brazilian shrimp farming uses mainly commercial feed for shrimp nutrition. This choice occurs because of the advantages related to convenience and good adaptation of Litopenaeus vannanmei to feed intake. Thus, the quality of feed is a determining factor for maximum performance of the shrimp farms, making the right selection of suppliers and control of the storage conditions as ways to prevent contamination and spoilage of feed. The objective of this study was to evaluate the stability of amino acids in meals and commercial feed with different protein levels, subjected to high-temperature storage. The samples were exposed to temperature of 50 oC and evaluated every 5 days for 30 days.The analyses of the degradation of amino acids were performed using an elution gradient in HPLC system.In evaluated meals it was observed that valine and arginine were the amino acids that suffered greater loss during the experiment and histidine and alanine suffered less degradation.Significant difference was observed in the content of all amino acids analyzed after exposure of the feed to the temperature of 50 oC; with reduce in values of its amino acid content. The results obtained in this study indicate that meals and feed exposed to elevated temperatures significantly reduced the content of its amino acids.

scholarly journals A Few Experimental Suggestions Using Minerals to Obtain Peptides with a High Concentration of L-Amino Acids and Protein Amino Acids

Symmetry ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2046
Author(s):  
Dimas A. M. Zaia ◽  
Cássia Thaïs B. V. Zaia
Keyword(s):  
Amino Acids ◽  
Rna World ◽  
High Concentration ◽  
Protein World ◽  
Protein Amino Acids ◽  
Hydrothermal Environment ◽  
World Hypothesis ◽  
Prebiotic Earth ◽  
Hydrothermal Environments ◽  
Selection Of

The peptides/proteins of all living beings on our planet are mostly made up of 19 L-amino acids and glycine, an achiral amino acid. Arising from endogenous and exogenous sources, the seas of the prebiotic Earth could have contained a huge diversity of biomolecules (including amino acids), and precursors of biomolecules. Thus, how were these amino acids selected from the huge number of available amino acids and other molecules? What were the peptides of prebiotic Earth made up of? How were these peptides synthesized? Minerals have been considered for this task, since they can preconcentrate amino acids from dilute solutions, catalyze their polymerization, and even make the chiral selection of them. However, until now, this problem has only been studied in compartmentalized experiments. There are separate experiments showing that minerals preconcentrate amino acids by adsorption or catalyze their polymerization, or separate L-amino acids from D-amino acids. Based on the [GADV]-protein world hypothesis, as well as the relative abundance of amino acids on prebiotic Earth obtained by Zaia, several experiments are suggested. The main goal of these experiments is to show that using minerals it is possible, at least, to obtain peptides whose composition includes a high quantity of L-amino acids and protein amino acids (PAAs). These experiments should be performed using hydrothermal environments and wet/dry cycles. In addition, for hydrothermal environment experiments, it is very important to use one of the suggested artificial seawaters, and for wet/dry environments, it is important to perform the experiments in distilled water and diluted salt solutions. Finally, from these experiments, we suggest that, without an RNA world or even a pre genetic world, a small peptide set could emerge that better resembles modern proteins.

scholarly journals SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure

2019 ◽  
Vol 24 (9) ◽  
pp. 928-938 ◽  
Author(s):  
Luca Palazzolo ◽  
Chiara Paravicini ◽  
Tommaso Laurenzi ◽  
Sara Adobati ◽  
Simona Saporiti ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Amino Acid Residues ◽  
Dibasic Amino Acid ◽  
Novel Target ◽  
Function Relationship ◽  
Dynamics Simulations

SLC6A14 (ATB0,+) is a sodium- and chloride-dependent neutral and dibasic amino acid transporter that regulates the distribution of amino acids across cell membranes. The transporter is overexpressed in many human cancers characterized by an increased demand for amino acids; as such, it was recently acknowledged as a novel target for cancer therapy. The knowledge on the molecular mechanism of SLC6A14 transport is still limited, but some elegant studies on related transporters report the involvement of the 12 transmembrane α-helices in the transport mechanism, and describe structural rearrangements mediated by electrostatic interactions with some pivotal gating residues. In the present work, we constructed a SLC6A14 model in outward-facing conformation via homology modeling and used molecular dynamics simulations to predict amino acid residues critical for substrate recognition and translocation. We docked the proteinogenic amino acids and other known substrates in the SLC6A14 binding site to study both gating regions and the exposed residues involved in transport. Interestingly, some of these residues correspond to those previously identified in other LeuT-fold transporters; however, we could also identify a novel relevant residue with such function. For the first time, by combined approaches of molecular docking and molecular dynamics simulations, we highlight the potential role of these residues in neutral amino acid transport. This novel information unravels new aspects of the human SLC6A14 structure–function relationship and may have important outcomes for cancer treatment through the design of novel inhibitors of SLC6A14-mediated transport.

scholarly journals Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics

Amino Acids ◽  
2020 ◽  
Vol 52 (9) ◽  
pp. 1207-1226
Author(s):  
Yun Ding ◽  
Joey Paolo Ting ◽  
Jinsha Liu ◽  
Shams Al-Azzam ◽  
Priyanka Pandya ◽  
...  
Keyword(s):  
Amino Acids ◽  
Its Sequence ◽  
Peptide Therapeutics ◽  
Large Proteins ◽  
Drug Candidates ◽  
Ongoing Development ◽  
The Stability ◽  
Natural Amino Acids ◽  
The Impact ◽  
As Toxicity

Abstract With the development of modern chemistry and biology, non-proteinogenic amino acids (NPAAs) have become a powerful tool for developing peptide-based drug candidates. Drug-like properties of peptidic medicines, due to the smaller size and simpler structure compared to large proteins, can be changed fundamentally by introducing NPAAs in its sequence. While peptides composed of natural amino acids can be used as drug candidates, the majority have shown to be less stable in biological conditions. The impact of NPAA incorporation can be extremely beneficial in improving the stability, potency, permeability, and bioavailability of peptide-based therapies. Conversely, undesired effects such as toxicity or immunogenicity should also be considered. The impact of NPAAs in the development of peptide-based therapeutics is reviewed in this article. Further, numerous examples of peptides containing NPAAs are presented to highlight the ongoing development in peptide-based therapeutics.

scholarly journals Democracy, ethnoicracy and consociational demoicracy

2019 ◽  
Vol 41 (1) ◽  
pp. 30-43
Author(s):  
Nenad Stojanović
Keyword(s):  
Ethnic Groups ◽  
Liberal Democracy ◽  
Stability Problem ◽  
Weak Form ◽  
Conceptual Level ◽  
Consociational Democracy ◽  
The Stability ◽  
Shaky Ground

This article questions the notion of ‘consociational democracy’. It argues that it rests on shaky ground, empirically and conceptually. As an empirical matter, a consociation is inherently unstable because it tends either to collapse into ethnoicracy (where the power is shared by the main ethnic groups so that citizens who do not belong to them are politically marginalized) or to become a non-consociational, liberal democracy. At the conceptual level ‘consociational democracy’ is an impossibility because a polity cannot be both consociational and democratic. This article argues that consociations can be at best demoicracies – that is, polities composed not of a single demos but of multiple demoi. Yet the problem of stability remains. The article concludes with the suggestion that the stability problem can be addressed by adopting a weak form of demoicracy – the ‘demoi-within-demos’ constellation – where a thin demos coexists with multiple demoi.

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