Scaling and self-organized criticality in proteins II

Phillips, J. C.

doi:10.1073/pnas.0811308105

Cited by 33 publications

(68 citation statements)

References 28 publications

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“…Interestingly, our water density analysis also showed that the solvent density is low in the Ran binding sites, revealing the fact that hydrophobic forces are important for RanGTP binding to Exp5 (Fig. 15A, left; Phillips 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Such an asymmetric distribution of water would principally buffer the electrostatic repulsions between phosphate groups of RNA and the electronegative atoms on the protein (Reddy et al 2001). For the Ran binding surfaces, the lower hydrophilic nature suggests that hydrophobic interactions play important roles in RanGTP binding to Exp5 (Phillips 2008). 3.…”

Section: Water Distribution Analysis Of the Inner And Outer Sides Ofmentioning

confidence: 99%

“…To explore the dynamical properties of Ran in the GTP state and the GDP state, we made a comparison between the Exp5-GTP-RNA and Exp5-GDP-RNA systems. To begin with, we investigated the hydrophobic contacts between Ran and Exp5 in both systems, which have been identified to play an important role in the stability of proteins (Phillips 2008), and found that the buried hydrophobic surface area of RanGTP complex is smaller (z100 Å 2 ) than that of RanGDP, which implies that RanGDP is more thermodynamically stable than RanGTP. By taking an average value for the enhancement of stability upon burial of the hydrophobic surface area (Vallone et al 1998), we estimated a contribution of z7 kJ/mol to thermodynamic stability in the RanGDP complex, and of 0 kJ/mol to RanGTP.…”

Section: Gtp Hydrolysis Undermines the Reassembly Of Ran To Exp5 In Cmentioning

confidence: 99%

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Dynamic mechanisms for pre-miRNA binding and export by Exportin-5

Wang¹,

Xue²,

Zhi³

et al. 2011

RNA

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The biogenesis and function of mature microRNAs (miRNAs) is dependent on the nuclear export of miRNA precursors (premiRNA) by . To characterize the molecular mechanisms of how pre-miRNA is recognized and transported by Exp5, we have performed 21 molecular dynamic (MD) simulations of RNA-bound Exp5 (Exp5-RanGTP-premiRNA, Exp5-RanGDP-premiRNA, Exp5-premiRNA), RNA-unbound Exp5 (Exp5-RanGTP, Exp5-RanGDP, apo-Exp5), and pre-miRNA. Our simulations with standard MD, steered molecular dynamics (SMD), and energy analysis have shown that (1) Free Exp5 undergoes extensive opening motion, and in this way facilitates the RanGTP binding. (2) RanGTP efficiently regulates the association/dissociation of pre-miRNA to its complex by inducing conformational changes in the HEAT-repeat helix stacking of Exp5. (3) The GTP hydrolysis prevents Ran from rebinding to Exp5 by regulating the hydrophobic interfaces and salt bridges between Ran and Exp5. (4) The transition from the A9-form to the A-form of the pre-miRNA modulates the structural complementarities between the protein and the pre-miRNA, thus promoting efficient assembly of the complex. (5) The baseflipping process (from the closed to the fully flipped state) of the 2-nt 39 overhang is a prerequisite for the pre-miRNA recognition by Exp5, which occurs in a sequence-independent manner as evidenced by the fact that different 2-nt 39 overhangs bind to Exp5 in essentially the same way. And finally, a plausible mechanism of the pre-miRNA export cycle has been proposed explaining how the protein-protein and protein-RNA interactions are coordinated in physiological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Water Distribution Analysis Of the Inner And Outer Sides Ofmentioning

confidence: 99%

Section: Gtp Hydrolysis Undermines the Reassembly Of Ran To Exp5 In Cmentioning

confidence: 99%

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Dynamic mechanisms for pre-miRNA binding and export by Exportin-5

Wang¹,

Xue²,

Zhi³

et al. 2011

RNA

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“…However, this does not mean that these small (but very numerous) interactions are unimportant; quite the contrary, they can easily connect the mutational and dynamical conformational differences and provide much more accurate and readily available estimates [7] of property trends than backbone strain energies, which are also long-range [9]. …”

Section: Introductionmentioning

confidence: 99%

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

Phillips

2014

BioMed Research International

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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.

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“…For the reader's convenience, the MZ and KD reordered BLOSUM62 matrices, as well as the MZ and KD diagonal mutation wave tables, are attached to this paper at arXiv xxx. The MZ and KD Ψ tables are in [15]. .…”

mentioning

confidence: 99%

Hidden thermodynamic information in protein amino acid mutation tables

Phillips

2017

Physica A: Statistical Mechanics and its Applications

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We combine the standard 1992 20x20 substitution matrix based on block alignment, BLOSUM62, with the standard 1982 amino acid hydropathicity scale KD as well as Protein amino acid sequences (aas) are rich in information, especially when combined with structural data. There are many Web-based tools for analyzing aas, but by far the most utilized is BLAST (Basic Local Alignment Search Tool), which compares two given sequences, or searches for sequences similar to a given sequence. The original BLAST paper[1] was the most highly cited paper published in the 1990s. A key BLAST element is the "substitution matrix", which assigns a score for aligning any possible pair of residues, and identifies "positive" mutations between similar aas. The BLOSUM62 matrix (available online) is the default for most BLAST programs [2]. It obtains mutation rates Γ of aa pairs from protein blocks (distantly related but conserved regions), which leads to accurate homological lists of functionally similar protein blocks.Competing effects of hydrophobic and hydrophilic segments of a given protein have long been known to be the primary driving force behind the folding of protein chains into protein globules. There are secondary effects associated with longitudinal hydrogen bonding (α helices) and transverse hydrogen bonding (β strands), and even weaker charge effects, but in most proteins the dominant physico-chemical factor in a kinetic property such as aggregation [3] is hydropathic interactions.

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Scaling and self-organized criticality in proteins II

Cited by 33 publications

References 28 publications

Dynamic mechanisms for pre-miRNA binding and export by Exportin-5

Dynamic mechanisms for pre-miRNA binding and export by Exportin-5

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

Hidden thermodynamic information in protein amino acid mutation tables

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