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1.
Eur Phys J E Soft Matter ; 44(11): 132, 2021 Oct 30.
Article in English | MEDLINE | ID: mdl-34718875

ABSTRACT

Understanding the physical and chemical properties of viral infections at molecular scales is a major challenge for the scientific community more so with the outbreak of global pandemics. There is currently a lot of effort being placed in identifying molecules that could act as putative drugs or blockers of viral molecules. In this work, we computationally explore the importance in antiviral activity of a less studied class of molecules, namely surfactants. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the phospholipid lecithin (POPC), in water. Our microsecond simulations show a preferential binding of lecithin to the receptor-binding motif of SARS-CoV-2 with binding free energies significantly larger than [Formula: see text]. Furthermore, hydrophobic interactions involving lecithin non-polar tails dominate these binding events, which are also accompanied by dewetting of the receptor binding motif. Through an analysis of fluctuations in the radius of gyration of the receptor-binding domain, its contact maps with lecithin molecules, and distributions of water molecules near the binding region, we elucidate molecular interactions that may play an important role in interactions involving surfactant-type molecules and viruses. We discuss our minimal computational model in the context of lecithin-based liposomal nasal sprays as putative mitigating therapies for COVID-19.


Subject(s)
Lecithins/chemistry , Molecular Docking Simulation , Phosphatidylcholines/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Surface-Active Agents/chemistry , Binding Sites , Hydrophobic and Hydrophilic Interactions , Nasal Sprays , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
2.
FEBS Lett ; 591(10): 1437-1451, 2017 05.
Article in English | MEDLINE | ID: mdl-28391640

ABSTRACT

The heterogeneity of computationally predicted reaction fluxes in metabolic networks within a single flux state can be exploited to detect their significant flux backbone. Here, we disclose the backbone of Escherichia coli, and compare it with the backbones of other bacteria. We find that, in general, the core of the backbones is mainly composed of reactions in energy metabolism corresponding to ancient pathways. In E. coli, the synthesis of nucleotides and the metabolism of lipids form smaller cores which rely critically on energy metabolism. Moreover, the consideration of different media leads to the identification of pathways sensitive to environmental changes. The metabolic backbone of an organism is thus useful to trace simultaneously both its evolution and adaptation fingerprints.


Subject(s)
Escherichia coli/growth & development , Metabolic Networks and Pathways , Systems Biology/methods , Algorithms , Bacteria/metabolism , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Models, Biological
3.
J R Soc Interface ; 12(110): 0543, 2015 Sep 06.
Article in English | MEDLINE | ID: mdl-26289659

ABSTRACT

Experimental and empirical observations on cell metabolism cannot be understood as a whole without their integration into a consistent systematic framework. However, the characterization of metabolic flux phenotypes is typically reduced to the study of a single optimal state, such as maximum biomass yield that is by far the most common assumption. Here, we confront optimal growth solutions to the whole set of feasible flux phenotypes (FFPs), which provides a benchmark to assess the likelihood of optimal and high-growth states and their agreement with experimental results. In addition, FFP maps are able to uncover metabolic behaviours, such as aerobic fermentation accompanying exponential growth on sugars at nutrient excess conditions, that are unreachable using standard models based on optimality principles. The information content of the full FFP space provides us with a map to explore and evaluate metabolic behaviour and capabilities, and so it opens new avenues for biotechnological and biomedical applications.


Subject(s)
Bacteria/metabolism , Biomass , Microbial Consortia/physiology , Models, Biological
4.
PLoS Comput Biol ; 10(5): e1003637, 2014 May.
Article in English | MEDLINE | ID: mdl-24854166

ABSTRACT

We unravel how functional plasticity and redundancy are essential mechanisms underlying the ability to survive of metabolic networks. We perform an exhaustive computational screening of synthetic lethal reaction pairs in Escherichia coli in a minimal medium and we find that synthetic lethal pairs divide in two different groups depending on whether the synthetic lethal interaction works as a backup or as a parallel use mechanism, the first corresponding to essential plasticity and the second to essential redundancy. In E. coli, the analysis of pathways entanglement through essential redundancy supports the view that synthetic lethality affects preferentially a single function or pathway. In contrast, essential plasticity, the dominant class, tends to be inter-pathway but strongly localized and unveils Cell Envelope Biosynthesis as an essential backup for Membrane Lipid Metabolism. When comparing E. coli and Mycoplasma pneumoniae, we find that the metabolic networks of the two organisms exhibit a large difference in the relative importance of plasticity and redundancy which is consistent with the conjecture that plasticity is a sophisticated mechanism that requires a complex organization. Finally, coessential reaction pairs are explored in different environmental conditions to uncover the interplay between the two mechanisms. We find that synthetic lethal interactions and their classification in plasticity and redundancy are basically insensitive to medium composition, and are highly conserved even when the environment is enriched with nonessential compounds or overconstrained to decrease maximum biomass formation.


Subject(s)
Adaptation, Physiological/physiology , Apoptosis/physiology , Cell Membrane/metabolism , Escherichia coli Proteins/metabolism , Escherichia coli/metabolism , Lipid Metabolism/physiology , Models, Biological , Cell Survival/physiology , Computer Simulation , Signal Transduction/physiology
5.
Sci Rep ; 2: 621, 2012.
Article in English | MEDLINE | ID: mdl-22934134

ABSTRACT

Mycoplasma pneumoniae is a human pathogen recently proposed as a genome-reduced model for bacterial systems biology. Here, we study the response of its metabolic network to different forms of structural stress, including removal of individual and pairs of reactions and knockout of genes and clusters of co-expressed genes. Our results reveal a network architecture as robust as that of other model bacteria regarding multiple failures, although less robust against individual reaction inactivation. Interestingly, metabolite motifs associated to reactions can predict the propagation of inactivation cascades and damage amplification effects arising in double knockouts. We also detect a significant correlation between gene essentiality and damages produced by single gene knockouts, and find that genes controlling high-damage reactions tend to be expressed independently of each other, a functional switch mechanism that, simultaneously, acts as a genetic firewall to protect metabolism. Prediction of failure propagation is crucial for metabolic engineering or disease treatment.


Subject(s)
Genome, Bacterial , Models, Biological , Pneumonia, Mycoplasma/genetics , Pneumonia, Mycoplasma/metabolism , Gene Expression Regulation, Bacterial , Gene Knockdown Techniques , Humans , Metabolic Networks and Pathways , Mutation , Stress, Physiological
7.
Phys Rev E Stat Nonlin Soft Matter Phys ; 81(1 Pt 1): 011402, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20365368

ABSTRACT

We study the propulsion of a micron-size paramagnetic colloidal doublet dispersed in water and driven above a surface by an external precessing magnetic field. The applied field forces the doublet to precess around an axis parallel to the plane of motion and the rotation of the colloidal assembly is rectified into translation due to a periodic asymmetry in dissipation close to the bounding plate. These recent experimental findings [P. Tierno, R. Golestanian, I. Pagonabarraga, and F. Sagués, Phys. Rev. Lett. 101, 218304 (2008)] are complemented here with a theoretical analysis of the system and extended to more complex magnetic modulations such as elliptical driving fields. Experimental results show a good agreement with numerical simulations with the aim to find the best conditions toward the optimization of propulsion speed and swimming efficiency.

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