Band 2, Heft 1

A classification of all possible icosahedral viral capsids is proposed. It takes into account the diversity of hexamers’ compositions, leading to definite capsid size.We showhowthe self-organization of observed capsids during their production results from definite symmetries of constituting hexamers. The division of all icosahedral capsids into four symmetry classes is given. New subclasses implementing the action of symmetry groups Z 2 , Z 3 and S 3 are found and described. They concern special cases of highly symmetric capsids whose T = p 2 + pq + q 2 -number is of particular type corresponding to the cases (p, 0) or (p, p).

It is well known that genomic materials (long DNA chains) of living organisms are often packed compactly under extreme confining conditions using macromolecular self-assembly processes but the general DNA packing mechanism remains an unsolved problem. It has been proposed that the topology of the packed DNA may be used to study the DNA packing mechanism. For example, in the case of (mutant) bacteriophage P4, DNA molecules packed inside the bacteriophage head are considered to be circular since the two sticky ends of the DNA are close to each other. The DNAs extracted from the capsid without separating the two ends can thus preserve the topology of the (circular) DNAs. It turns out that the circular DNAs extracted from bacteriophage P4 are non-trivially knotted with very high probability and with a bias toward chiral knots. In order to study this problem using a systematic approach based on mathematical modeling, one needs to introduce a DNA packing model under extreme volume confinement condition and test whether such a model can produce the kind of knot spectrum observed in the experiments. In this paper we introduce and study a model of equilateral random polygons con_ned in a sphere. This model is not meant to generate polygons that model DNA packed in a virus head directly. Instead, the average topological characteristics of this model may serve as benchmark data for totally randomly packed circular DNAs. The difference between the biologically observed topological characteristics and our benchmark data might reveal the bias of DNA packed in the viral capsids and possibly lead to a better understanding of the DNA packing mechanism, at least for the bacteriophage DNA. The purpose of this paper is to provide information about the knot spectrum of equilateral random polygons under such a spherical confinement with length and confinement ratios in a range comparable to circular DNAs packed inside bacteriophage heads.

Gramicidin A is a small and well characterized peptide that forms an ion channel in lipid membranes. An important feature of gramicidin A (gA) pore is that its conductance is affected by the electric charges near the its entrance. This property has led to the application of gramicidin A as a biochemical sensor for monitoring and quantifying a number of chemical and enzymatic reactions. Here, a mathematical model of conductance changes of gramicidin A pores in response to the presence of electrical charges near its entrance, either on membrane surface or attached to gramicidin A itself, is presented. In this numerical simulation, a two dimensional computational domain is set to mimic the structure of a gramicidin A channel in the bilayer surrounded by electrolyte. The transport of ions through the channel is modeled by the Poisson-Nernst-Planck (PNP) equations that are solved by Finite Element Method (FEM). Preliminary numerical simulations of this mathematical model are in qualitative agreement with the experimental results in the literature. In addition to the model and simulations, we also present the analysis of the stability of the solution to the boundary conditions and the convergence of FEM method for the two dimensional PNP equations in our model.

Modeling of repulsive forces is essential to the understanding of certain bio-physical processes, especially for the motion of DNA molecules. These kinds of phenomena seem to be driven by some sort of “energy” which especially prevents the molecules from strongly bending and forming self-intersections. Inspired by a physical toy model, numerous functionals have been defined during the past twenty-five years that aim at modeling self-avoidance. The general idea is to produce “detangled” curves having particularly large distances between distant strands. In this survey we present several families of these so-called knot energies. It turns out that they are quite similar from an analytical viewpoint. We focus on proving self-avoidance and existence of minimizers in every knot class. For a suitable subfamily of these energies we show how to prove that these minimizers are even infinitely differentiable.

We investigate the relationship between a discrete version of thickness and its smooth counterpart. These discrete energies are deffned on equilateral polygons with n vertices. It will turn out that the smooth ropelength, which is the scale invariant quotient of length divided by thickness, is the Γ-limit of the discrete ropelength for n → ∞, regarding the topology induced by the Sobolev norm ‖ · ‖ W 1,∞ (S 1 ,ℝ d ). This result directly implies the convergence of almost minimizers of the discrete energies in a fixed knot class to minimizers of the smooth energy.Moreover,we show that the unique absolute minimizer of inverse discrete thickness is the regular n-gon.

The Poisson-Boltzmann equation (PBE) is one important implicit solvent continuum model for calculating electrostatics of protein in ionic solvent. Several numerical algorithms and program packages have been developed but verification and comparison between them remains an interesting topic. In this paper, a PBE test model is presented for a protein in a spherical solute region, along with its analytical solution. It is then used to verify a PBE finite element solver and applied to a numerical comparison study between a finite element solver and a finite difference solver. Such a study demonstrates the importance of retaining the interface conditions in the development of PBE solvers.

Trypanosomatida parasites, such as Trypanosoma and Leishmania, are the cause of deadly diseases in many third world countries. The three dimensional structure of their mitochondrial DNA, known as kinetoplast DNA (kDNA), is unique since it is organized into several thousands of minicircles that are topologically linked. How and why the minicircles form such a network have remained unanswered questions. In our previous work we have presented a model of network formation that hypothesizes that the network is solely driven by the confinement of minicircles. Our model shows that upon confinement a percolation network forms. This network grows into a space filling network, called saturation network, upon further confinement of minicircles. Our model also shows, in agreement with experimental data, that the mean valence of the network (that is, the average number of minicircles topologically linked to any minicircle in the network) grows linearly with minicircle density. In our previous studies however we disregarded DNA flexibility and used rigid minicircles to model DNA, here we address this limitation by allowing minicircles to be flexible. Our numerical results show that the topological characteristics that describe the growth and topology of the minicircle networks have similar values to those observed in the case of rigid minicircles suggesting that these properties are robust and therefore a potentially adequate description of the networks observed in Trypanosomatid parasites.

Description of inhomogeneous dielectric properties of a solvent in the vicinity of ions has been attracting research interests in mathematical modeling for many years. From many experimental results, it has been concluded that the dielectric response of a solvent linearly depends on the ionic strength within a certain range. Based on this assumption, a new implicit solvent model is proposed in the form of total free energy functional and a quasi-linear Poisson-Boltzmann equation (QPBE) is derived. Classical Newton’s iteration can be used to solve the QPBE numerically but the corresponding Jacobian matrix is complicated due to the quasi-linear term. In the current work, a systematic formulation of the Jacobian matrix is derived. As an alternative option, an algorithm mixing the Newton’s iteration and the fixed point method is proposed to avoid the complicated Jacobian matrix, and it is a more general algorithm for equation with discontinuous coefficients. Computational efficiency and accuracy for these two methods are investigated based on a set of equation parameters. At last, the QPBE with singular charge source and piece-wisely defined dielectric functions has been applied to analyze electrostatics of macro biomolecules in a complicated solvent. A set of computational algorithms such as interface method, singular charge removal technique and the Newtonfixed- point iteration are employed to solve the QPBE. Biological applications of the proposed model and algorithms are provided, including calculation of electrostatic solvation free energy of proteins, investigation of physical properties of channel pore of an ion channel, and electrostatics analysis for the segment of a DNA strand.

Retrovirus capsid is a fullerene-like lattice consisting of capsid protein hexamers and pentamers. Mathematical models for the lattice structure help understand the underlying biological mechanisms in the formation of viral capsids. It is known that viral capsids could be categorized into three major types: icosahedron, tube, and cone. While the model for icosahedral capsids is established and well-received, models for tubular and conical capsids need further investigation. This paper proposes new models for the tubular and conical capsids based on an extension of the Capser-Klug quasi-equivalence theory. In particular, two and three generating vectors are used to characterize respectively the lattice structures of tubular and conical capsids. Comparison with published HIV-1 data demonstrates a good agreement of our modeling results with experimental data.

Polymerases select nucleotides according to a template before incorporating them for chemical synthesis during gene replication or transcription. Efficient selection to achieve sufficiently high fidelity and speed is essential for polymerase function. Due to multiple kinetic steps detected in a polymerase elongation cycle, there exist multiple selection checkpoints to allow different strategies of fidelity control. In our current work, we examined step-by-step selections in an elongation cycle that have conformational transition rates tuned one at a time, with a controlled differentiation free energy between the right and wrong nucleotides at each checkpoint. The elongation is sustained at non-equilibrium steady state with constant free energy input and heat dissipation. It is found that a selection checkpoint in the later stage of a reaction path has less capability for error reduction. Hence, early selection is essential to achieve an efficient fidelity control. In particular, for an intermediate state, the selection through the forward transition inhibition has the same capacity for error reduction as the selection through the backward rejection. As with respect to the elongation speed, an initial screening is indispensible for maintaining high speed, as the wrong nucleotides can be removed quickly and replaced by the right ones at the entry. Overall, the elongation error rate can be repeatedly reduced through multiple selection checkpoints. This study provides a theoretical framework to guide more detailed structural dynamics studies, and to support rational redesign of related enzymes and devices.