Punctuated Evolution of Influenza Virus Neuraminidase (A/H1N1) under Opposing Migration and Vaccination Pressures

Abstract

Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Here we focus first on the simpler problem of the much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. Our thermodynamic panorama shows that very small amino acid changes can be monitored very accurately across many historic (1945–2011) Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the fractal differential hydropathicity scale based on protein self-organized criticality (SOC). Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in common influenza severity in the last century. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses directly from amino acid sequences alone. An engineered strain of NA1 is described which could well be significantly less virulent than current circulating strains.

Oxygen channels and fractal wave–particle duality in the evolution of myoglobin and neuroglobin

“…Scaling, improved by inclusion of multiple individual factors, is likely to be an increasingly important tool in medical contexts [46,47]. At the molecular level it has already provided a detailed description of viral sequence evolution [48], which may well be more accurate in selecting suitable vaccine targets than antigenic clustering [49]. Because of the complexity of proteins and their interactions, economy, simplicity and universality are critical features of theoretical biophysical tools.…”

Fractals and self-organized criticality in proteins

“…This can guide us to choosing characteristic values of W , which appear to be smaller for more stable proteins (like the all-α heptad transmembrane opsins [10,35]), around W ∼ 21 for membraneassociated proteins, and larger (W ∼ 100) for adaptive proteins like lysozyme with large β regions. Mutation-prolific viral glycoproteins also have medium and large characteristic values of W [36].…”

“…However, the overall weight of Ref. [6]'s discovery of SOC through modularity, and its implications for addressing accurately protein functionality through globular roughness, represent an intriguing biological expansion of connectivity and fractal criticality [6,36]. There is some overlap between statistical similarity models [37] and hydromodel hierarchical analysis of visual opsins [34].…”

Thermodynamic Description of Beta Amyloid Formation Using Physicochemical Scales and Fractal Bioinformatic Scales

“…It is possible that the 3 aa width of this KD flat peak is accurate because fragmentation occurs at a high effective temperature. 17 The range covered by the NMR sandwich model of Figure 1 matches the abrupt increases of the MZ and KD ψ(aa,21) profiles near site 688. also explains the remarkable success of the MZ scale in Figure 3.…”