A Rate Distortion approach to protein symmetry

A spontaneous symmetry breaking argument is applied to the problem of protein form, via a Rate Distortion analysis of the relation between genome coding and the final condensation of the protein 'molten globule'. The Rate Distortion Function, under coding constraints, serves as a temperature analog, so that low values act to drive proteins to simple symmetries. The Rate Distortion Function itself is significantly constrained by the availability of metabolic free energy. This work extends Tlusty's (2007) elegant exploration of the evolution of the genetic code, suggesting that rate distortion considerations may play a critical role across a broad spectrum of molecular expressions of evolutionary process

Without magic bullets: the biological basis for public health interventions against protein folding disorders

Protein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding regulation under a cellular-level cognitive paradigm similar to that proposed by Atlan and Cohen (1998) for the immune system. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of regulatory failure, in essence, a premature aging driven by familiar synergisms between disjunctions of resource allocation and need in the context of socially or physiologically toxic exposures and chronic powerlessness at individual and group scales. Application of an HPA axis model is made to recent observed differences in Alzheimer's onset rates in White and African American subpopulations as a function of an index of distress-proneness

Protein folding disorders: Toward a basic biological paradigm

Mechanistic 'physics' models of protein folding fail to account for the observed spectrum of protein folding and aggregation disorders, suggesting that a more appropriately biological paradigm will be needed for understanding the etiology, prevention, and treatment of these diseases

`The frozen accident' as an evolutionary adaptation: A rate distortion theory perspective on the dynamics and symmetries of genetic coding mechanisms

We survey some interpretations and related issues concerning the frozen hypothesis due to F. Crick and how it can be explained in terms of several natural mechanisms involving error correction codes, spin glasses, symmetry breaking and the characteristic robustness of genetic networks. The approach to most of these questions involves using elements of Shannon's rate distortion theory incorporating a semantic system which is meaningful for the relevant alphabets and vocabulary implemented in transmission of the genetic code. We apply the fundamental homology between information source uncertainty with the free energy density of a thermodynamical system with respect to transcriptional regulators and the communication channels of sequence/structure in proteins. This leads to the suggestion that the frozen accident may have been a type of evolutionary adaptation

Empirical predictions of an intrinsically disordered protein theory approach to glycan/lectin reaction kinetics

Newly-developed methods from the theory of intrinsically disordered proteins can be applied to the flexible glycan structures that coat cellular surfaces and provide rich channels for biological information transmission. Extension of a mechanistic 'arm-in-sleeve' model via a nonrigid molecule symmetry analysis leads to expectation of empirical observation of punctuated 'spectral' classifications in glycan/lectin interaction, parameterized by an appropriate index of glycan frond length or other index of topological complexity, possibly requiring groupoid classifications analogous to quasicrystals

On the social induction of Alzheimer's disease: An index theorem aging model for amyloid formation

The central 'risk factor' for Alzheimer's disease (AD) is age. From first principles, we construct a mathematical model of protein folding and its in vivo regulation that gives this result in a natural manner. We extend the basic approach using topological information theory methods, and examine a case history of socially-induced premature aging in the United States

Extending Tlusty's method to the glycome: Tuning the repertoire of glycan determinants

We apply Tlusty's information-theoretic analysis of the genetic code to the glycome, using a cognitive paradigm in which external information sources constrain and tune the glycan code error network, in the context of available metabolic energy. The resulting dynamic model suggests the possibility of observing spontaneous symmetry breaking of the glycan code as a function of metabolic energy intensity. These effects may be currently present, or embedded in evolutionary trajectory, recording large-scale ecosystem resilience shifts in energy availability such as the aerobic transition

Beyond the fuzzy lock-and-key: spontaneous symmetry shifts and glycan/lectin logic gates

Changes in the molecular topology of glycan/lectin interaction may explain observed reaction punctuation driven by experimental gradients in reactant concentration. Adoption of a 'biological renormalization' perspective from statistical physics for the analysis of such phase transitions suggests, in marked contrast to conventional physical systems, a broad spectrum of possible universality class behaviors. This spectrum may, in typical perverse biological manner, be of central scientific interest. Generalization, via formalism abducted from coevolutionary theory, suggests that glycan/lectin molecular switches instantiate logic gates that may be as sophisticated as those characterizing basic neural process, if on a different scale

Metabolic constraints on the evolution of genetic codes: Did multiple 'preaerobic' ecosystem transitions entrain richer dialects via Serial Endosymbiosis?

A mathematical model based on Tlusty's topological deconstruction suggests that multiple punctuated ecosystem shifts in available metabolic free energy, broadly akin to the 'aerobic' transition, enabled a punctuated sequence of increasingly complex genetic codes and protein translators under mechanisms similar to the Serial Endosymbiosis effecting the Eukaryotic transition. These evolved until the ancestor to the present narrow spectrum of nearly maximally robust codes became locked-in by path dependence

Systemic lupus erythematosus in African-American women: immune cognitive modules, autoimmune disease, and pathogenic social hierarchy

Examining elevated rates of systemic lupus erythematosus in African-American women from the perspective of the emerging theory of immune cognition suggests the disease constitutes an internalized physiological image of external patterns of psychosocial stress, a 'pathogenic social hierarchy' involving the synergism of racism and gender discrimination. The disorder represents the punctuated resetting of 'normal' immune self-image to a self-attacking 'excited' state, a process formally analogous to models of punctuated equilibrium in evolutionary theory. We speculate that this punctuated onset takes place in the context of an immunological 'cognitive module' similar to what has been proposed by evolutionary psychologists for the human mind. We discuss the broader implications of a high rate of this disorder within a marginalized population, finding it to be a leading indicator for phenomena likely to entrain powerful subgroups into a larger pattern of embedding patholog