Volume 6, Issue 1

Many viral capsids follow an icosahedral fullerene-like structure, creating a caged polyhedral arrangement built entirely from hexagons and pentagons. Viral capsids consist of capsid proteins,which group into clusters of six (hexamers) or five (pentamers). Although the number of hexamers per capsid varies depending on the capsid size, Caspar-Klug Theory dictates there are exactly twelve pentamers needed to form a closed capsid.However, for a significant number of viruses, including viruses of the Papovaviridae family, the theory doesn’t apply. The anomaly of the Caspar-Klug Theory has raised a new question:“For which Caspar and Klug models can each hexamer be replaced with a pentamer while still following icosahedral symmetry?” This paper proposes an answer to this question by examining icosahedral viral capsid-like structures composed only of pentamers, called pentagonal polyhedra. The analysis shows that pentagonal polyhedra fall in a subclass of T, defined by P ≥ 7 and T = 1( mod 3).

A quasi-one-dimensional steady-state Poisson-Nernst-Planck model of two oppositely charged ion species through a membrane channel is analyzed. The model problem is treated as a boundary value problem of a singularly perturbed differential system. Our analysis is based on the geometric singular perturbation theory but, most importantly, on specific structures of this concrete model. The existence and (local ) uniqueness of solutions to the boundary value problem is established. In particular, an approximation of both the individual flux and the I-V (current-voltage) relation are derived explicitly from the zeroth order approximation (in ") solutions, from which the boundary layer effects on ionic flows are studied in great details.

In this work, we consider ionic flow through ion channels for an ionic mixture of a cation species (positively charged ions) and an anion species (negatively charged ions), and examine effects of a positive permanent charge on fluxes of the cation species and the anion species. For an ion species, and for any given boundary conditions and channel geometry,we introduce a ratio _(Q) = J(Q)/J(0) between the flux J(Q) of the ion species associated with a permanent charge Q and the flux J(0) associated with zero permanent charge. The flux ratio _(Q) is a suitable quantity for measuring an effect of the permanent charge Q: if _(Q) > 1, then the flux is enhanced by Q; if _ < 1, then the flux is reduced by Q. Based on analysis of Poisson-Nernst-Planck models for ionic flows, a universal property of permanent charge effects is obtained: for a positive permanent charge Q, if _1(Q) is the flux ratio for the cation species and _2(Q) is the flux ratio for the anion species, then _1(Q) < _2(Q), independent of boundary conditions and channel geometry. The statement is sharp in the sense that, at least for a given small positive Q, depending on boundary conditions and channel geometry, each of the followings indeed occurs: (i) _1(Q) < 1 < _2(Q); (ii) 1 < _1(Q) < _2(Q); (iii) _1(Q) < _2(Q) < 1. Analogous statements hold true for negative permanent charges with the inequalities reversed. It is also shown that the quantity _(Q) = |J(Q) − J(0)| may not be suitable for comparing the effects of permanent charges on cation flux and on anion flux. More precisely, for some positive permanent charge Q, if _1(Q) is associated with the cation species and _2(Q) is associated with the anion species, then, depending on boundary conditions and channel geometry, each of the followings is possible: (a) _1(Q) > _2(Q); (b) _1(Q) < _2(Q).

Single channel dynamics can be modeled using stochastic differential equations, and the dynamics of the state of the channel (e.g. open, closed, inactivated) can be represented using Markov models. Such models can also be used to represent the effect of mutations as well as the effect of drugs used to alleviate deleterious effects of mutations. Based on the Markov model and the stochastic models of the single channel, it is possible to derive deterministic partial differential equations (PDEs) giving the probability density functions (PDFs) of the states of the Markov model. In this study, we have analyzed PDEs modeling wild type (WT) channels, mutant channels (MT) and mutant channels for which a drug has been applied (MTD). Our aim is to show that it is possible to optimize the parameters of a given drug such that the solution of theMTD model is very close to that of the WT: the mutation’s effect is, theoretically, reduced significantly.We will present the mathematical framework underpinning this methodology and apply it to several examples. In particular, we will show that it is possible to use the method to, theoretically, improve the properties of some well-known existing drugs.