抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

http://www.tau.ac.il/lifesci/courses/molecular_biophysics/3745.pdf

Imaging α-Hemolysin with Molecular Dynamics: Ionic Conductance, Osmotic Permeability, and the Electrostatic Potential Map

Theoretical Methods for the Description of the Solvent Effect in Biomolecular Systems.

With the continued improvement of sequencing technologies, the prospect of genome-based medicine is now at the forefront of scientific research. To realize this potential, however, a revolutionary sequencing method is needed for the cost-effective and rapid interrogation of individual genomes. This capability is likely to be provided by a physical approach to probing DNA at the single-nucleotide level. This is in sharp contrast to current techniques and instruments that probe (through chemical elongation, electrophoresis, and optical detection) length differences and terminating bases of strands of DNA. Several physical approaches to DNA detection have the potential to deliver fast and low-cost sequencing. Central to these approaches is the concept of nanochannels or nanopores, which allow for the spatial confinement of DNA molecules. In addition to their possible impact in medicine and biology, the methods offer ideal test beds to study open scientific issues and challenges in the relatively unexplored area at the interface between solids, liquids, and biomolecules at the nanometer length scale. This Colloquium emphasizes the physics behind these methods and ideas, critically describes their advantages and drawbacks, and discusses future research opportunities in the field.

/pdf/colloquium-physical-approaches-to-dna-sequencing-and-apsgzh060l.pdf

Colloquium: Physical approaches to DNA sequencing and detection

Pharmacology of Acute PainNMDA receptor subunits: Function and pharmacology

http://atto.tau.ac.il/~nitzan/pnp-maria.pdf

A Lattice Relaxation Algorithm for Three-Dimensional Poisson-Nernst-Planck Theory with Application to Ion Transport through the Gramicidin A Channel

Three-Dimensional Poisson-Nernst-Planck Theory Studies: Influence of Membrane Electrostatics on Gramicidin A Channel Conductance

The Poisson-Nernst-Planck (PNP) theory of electro-diffusion is reviewed. Techniques for numerical solution of the three-dimensional PNP equations are summarized, and several illustrative applications to ion transport through protein channels are presented. Strengths and weaknesses of the theory are discussed, as well as attempts to improve it via increasingly realistic evaluation of the force acting on each ion due to the protein/membrane environment.

Poisson-Nernst-Planck theory approach to the calculation of current through biological ion channels

The role of the dielectric barrier in narrow biological channels: a novel composite approach to modeling single-channel currents.

Simulations of ion permeation through narrow model cylindrical channels are carried out using a dynamic lattice Monte Carlo (DLMC) algorithm (equivalent to high friction Langevin dynamics) for the time evolution of the ions in the system on the basis of a careful evaluation of the electrostatic forces acting upon each particle. To mimic the process of ion transport through protein channels, the cylindrical channel is embedded in a dielectric slab (representing a lipid bilayer membrane). The protein/membrane structure is taken to be rigid, and the water solvent is treated as a dielectric continuum. Results of these simulations are compared to corresponding results obtained via Poisson-Nernst-Planck (PNP) theory. In the PNP approach, the mobile ions are treated as a continuous charge density, and the electrostatic force on each ion is treated in an approximate fashion. Significant differences between DLMC and PNP results are found, with the degree of discrepancy increasing as the radius of the ion channel is reduced. A major source of error is traced to the neglect in the effective PNP potential of the dielectric self-energy (DSE), which is due to the interaction of each permeant ion with the dielectrically inhomogeneous environment provided by the water/channel/membrane system. When this static single-particle potential is precalculated and added to the effective potential used in PNP theory, substantial improvement in the quality of the results for current -voltage curves and steady-state concentrations is obtained. In fact, the results obtained by this approach, termed dielectric self-energy Poisson Nernst-Planck (DSEPNP) theory, agree nearly quantitatively with DLMC simulation results over the entire range of channel radii (4-12 A) studied.

/pdf/comparison-of-dynamic-lattice-monte-carlo-simulations-and-4vf1ji1jx9.pdf

Maria Kurnikova

Papers

A Lattice Relaxation Algorithm for Three-Dimensional Poisson-Nernst-Planck Theory with Application to Ion Transport through the Gramicidin A Channel

Three-Dimensional Poisson-Nernst-Planck Theory Studies: Influence of Membrane Electrostatics on Gramicidin A Channel Conductance

Poisson-Nernst-Planck theory approach to the calculation of current through biological ion channels

The role of the dielectric barrier in narrow biological channels: a novel composite approach to modeling single-channel currents.

Comparison of Dynamic Lattice Monte Carlo Simulations and the Dielectric Self-Energy Poisson-Nernst-Planck Continuum Theory for Model Ion Channels