Charged amino acids may promote coronavirus SARS-CoV-2 fusion with the host ce

The charged amino acids in the spike protein of SARS-CoV-2 exhibit some specific distribution. In the RBD region of the S1 unit the positive charge dominates in the protein interior and the negative charge prevails on the surface exposed towards ACE2 receptor. The charged amino acids in the S2 region preceding heptad repeats of the spike protein of SARS-CoV-2, exhibit a central concentration, and the imbalance of a positive charge. The idea that both distributions of charged amino acids may, in an electrostatic manner, facilitate the coronavirus infection of the cell is presented. An evaluation of the virus-receptor binding energy, by docking the peptide resembling the human receptor site to the virus RBD, and the estimation of electromechanical deformation of the cell membrane by S2 during the prefusion process were included. Possible prevention of viral infection is suggested

The Smooth Evolution of the Universal Genetic Code. Main Episodes

The possible scenario of the origin and evolution of genetic code is proposed, being primarily implicated by the working hypothesis which states that the chronological order of amino acids evolutionary implementation monotonically correlates with their increasing mass. It fulfills the minimalistic claim of the smallest changes of the evolving system at increasing complexity, hereinafter called "the smooth evolution". The working hypothesis was postulated concerning the results of statistical analysis indicating a strong correlation between amino acid mass and the chosen parameters of contemporary genetic code, which are expected to change in a certain individual direction during the evolution of the initial genetic system. It was additionally supplemented by the most common hypotheses adopted from the literature, as stereochemical, 'frozen accident' and coevolutional. The developed scenario allows a detailed description of the twenty-two consecutive episodes of the history of code definition and the estimation of its dynamics. It reveals the main eras of evolution conditioned by the environmental and structural constraints. It also lets the estimation of the evolutionary frequencies of codon sense expansion, and redefinition. Dominating trends and amino acids were indicated. The underlying assumptions, limits, exceptions, and the future of the code evolution have been discusse

Rotational-electric principles of RNA/DNA and viability

: Photographic investigations of rising bubbles in seawater revealed that each bubble may conduct a single or bi-spiraling motion, which resemble architecture of RNA or DNA respectively. The rotational motion results from acceleration of ionic hydrates, which are separated to anionic and cationic domains at the upper and bottom curvatures of the bubble. Afterwards, rotational motion undergoes further acceleration in the bubble upper vortex, followed by deceleration at the vortex tip. During that phase, the spiraling motion cause significant friction that result in polarization of electronegative atoms of H, C, N, O and P. These may be simultaneously arranged around a whirling cationic strands and form phosphate groups, ribose and nitrogen bases equipped with H2 and H3 rotors. It is hypothesized that such hydrogen rotors may operate as generators of electrons, which may be detached from valence shells of electropositive atoms. Then, electrons may flow via nitrogen bases and deoxyribose or ribose to phosphate groups. Next, the negatively charged edges of phosphate groups may attract cationic hydrates and energize their rotational motion in the grooves, then causing also its spiraling projection outward. That may be responsible for replication of nucleotides and its arrangement along the cationic flow into RNA or DNA polymers, in the same manner as originally produced by rising bubbles. Moreover, it points that hydrogen rotors may generate energy needed for viability as well as interact with all physical and chemical fields

Combined in silico and 19F NMR analysis of 5-fluorouracil metabolism in yeast at low ATP conditions.

The cytotoxic effect of 5-fluorouracil (5-FU) on yeast cells is thought to be mainly via a misincorporation of fluoropyrimidines into both RNA and DNA, not only DNA damage via inhibition of thymidylate synthase (TYMS) by fluorodeoxyuridine monophosphate (FdUMP). However, some studies on Saccharomyces cerevisiae show a drastic decrease in ATP concentration under oxidative stress, together with a decrease in concentration of other tri- and diphosphates. This raises a question if hydrolysis of 5-fluoro-2-deoxyuridine diphosphate (FdUDP) under oxidative stress could not lead to the presence of FdUMP and the activation of so-called ‘thymine-less death’ route. We attempted to answer this question with in silico modeling of 5-FU metabolic pathways, based on new experimental results, where the stages of intracellular metabolism of 5-FU in Saccharomyces cerevisiae were tracked by a combination of 19F and 31P NMR spectroscopic study. We have identified 5-FU, its nucleosides and nucleotides, and subsequent di- and/or triphosphates. Additionally, another wide 19F signal, assigned to fluorinated unstructured short RNA, has been also identified in the spectra. The concentration of individual metabolites was found to vary substantially within hours,however,theinitialsteady-statewaspreservedonlyforanhour,untiltheATPconcentration dropped by a half, which was monitored independently via 31P NMR spectra. After that, the catabolic process leading from triphosphates through monophosphates and nucleosides back to 5-FU was observed. These results imply careful design and interpretation of studies in 5-FU metabolism in yeast

Theoretical model explaining the relationship between the molecular mass and the activation energy of the enzyme revealed by a large-scale analysis of bioinformatics data.

A general dependence of the enzyme catalytic rate on its mass was revealed when a statistical analysis of 17065 records from the EMP database was performed. The estimated activation energy of the catalytic process decreases asymptotically with the enzyme molecular mass increase. The proposed theoretical model postulates the existence of an intermediate complex of the enzyme and the departing product. It allows for the explanation of the discovered mass-energy relationship, as an effect of the global enzyme-product interactions during complex dissociation. Fitted parameters of the model seem to be in agreement with those widely accepted for the van der Waals energy of molecular interactions. Their values also agree with the picture of the hydrogen bonding in the catalytic process and suggest that surface walk can be the favorable way of the product departure

A kinetic model of the evolution of a protein interaction network

Abstract Background: Known protein interaction networks have very particular properties. Old proteins tend to have more interactions than new ones. One of the best statistical representatives of this property is the node degree distribution (distribution of proteins having a given number of interactions). It has previously been shown that this distribution is very close to the sum of two distinct exponential components. In this paper, we asked: What are the possible mechanisms of evolution for such types of networks? To answer this question, we tested a kinetic model for simplified evolution of a protein interactome. Our proposed model considers the emergence of new genes and interactions and the loss of old ones. We assumed that there are generally two coexisting classes of proteins. Proteins constituting the first class are essential only for ecological adaptations and are easily lost when ecological conditions change. Proteins of the second class are essential for basic life processes and, hence, are always effectively protected against deletion. All proteins can transit between the above classes in both directions. We also assumed that the phenomenon of gene duplication is always related to ecological adaptation and that a new copy of a duplicated gene is not essential. According to this model, all proteins gain new interactions with a rate that preferentially increases with the number of interactions (the rich get richer). Proteins can also gain interactions because of duplication. Proteins lose their interactions both with and without the loss of partner genes. Results: The proposed model reproduces the main properties of protein-protein interaction networks very well. The connectivity of the oldest part of the interaction network is densest, and the node degree distribution follows the sum of two shifted power-law functions, which is a theoretical generalization of the previous finding. The above distribution covers the wide range of values of node degrees very well, much better than a power law or generalized power law supplemented with an exponential cut-off. The presented model also relates the total number of interactome links to the total number of interacting proteins. The theoretical results were for the interactomes of A. thaliana, B. taurus, C. elegans, D. melanogaster, E. coli, H. pylori, H. sapiens, M. musculus, R.norvegicus and S. cerevisiae. Conclusions: Using these approaches, the kinetic parameters could be estimated. Finally, the model revealed the evolutionary kinetics of proteome formation, the phenomenon of protein differentiation and the process of gaining new interactions

SARS-CoV-2 variant Omicron (B.1.1.529) is in a rising trend of mutations increasing the positive electric charge in crucial regions of the spike protein S

An increase in the positive electric charge of SARS-CoV-2 variant Omicron (B.1.1.529) was reported and the elec�trostatic interaction between the spike protein S and ACE2 receptor was estimated. The results presented here suggest that electrogenic mutations in specific regions of the S protein and the electrostatic force may facilitate viral infection of the host cell

Additional Positive Electric Residues in the Crucial Spike Glycoprotein S Regions of the New SARS-CoV-2 Variants

The change in the formal charge of 34 SARS-CoV-2 lineages from September 2020 to June 2021 was analyzed according to the monthly evidence of the European agency. The reported point mutations and small insertions are electrically neutral (17), positive (12), or negative (3). They had been found in the spike glycoprotein S, in the RBD and S1/S2 regions, crucial for initiation of viral infection. The most often observed were positive mutations, especially D614G and E484K, located in the region of S1/S2 junction, and in the receptor-binding domain (RBD), respectively. They are related to G and A switching. Positive mutations are stretching equally in both areas, but in the RBD region, they are more dispersed. In the set of analyzed virus variants, the increasing tendency in the number of positively charged residues in spike protein was observed. Furthermore, the well-documented WHO classes show an increase in the COVID-19 percentage case fatality with the positive increase in the spike crucial region’s total charge. The data mining, applying classifier algorithm based on the artificial neuronal network, confirms that the value and the distribution of additional positive charge in S may be important factors enabling virus impact to immunity. This may be promoted by the stronger long-range electrostatic attraction of the virus particle to the host cell, preceding the infection. The estimation of the potential energy for the RBD approaching the angiotensin-converting enzyme (ACE2) was presented

The quantum casimir effect may be a universal force organizing the bilayer structure of the cell membrane.

A mathematic-physical model of the interaction between cell membrane bilayer leaflets is proposed based on the Casimir effect in dielectrics. This model explains why the layers of a lipid membrane gently slide one past another rather than penetrate each other. The presented model reveals the dependence of variations in the free energy of the system on the membrane thickness. This function is characterized by the two close minima corresponding to the different levels of interdigitation of the lipids from neighbor layers. The energy barrier of the compressing transition between the predicted minima is estimated to be 5.7 kT/lipid, and the return energy is estimated to be 3.1 kT/lipid. The proposed model enables estimation of the value of the membrane elastic thickness modulus of compressibility, which is 1.7 × 10(9) N/m(2), and the value of the interlayer friction coefficient, which is 1.9 × 10(8) Ns/m(3)