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

A novel and robust automated docking method that predicts the bound conformations of flexible ligands to macromolecular targets has been developed and tested, in combination with a new scoring function that estimates the free energy change upon binding. Interestingly, this method applies a Lamarckian model of genetics, in which environmental adaptations of an individual's phenotype are reverse transcribed into its genotype and become . heritable traits sic . We consider three search methods, Monte Carlo simulated annealing, a traditional genetic algorithm, and the Lamarckian genetic algorithm, and compare their performance in dockings of seven protein)ligand test systems having known three-dimensional structure. We show that both the traditional and Lamarckian genetic algorithms can handle ligands with more degrees of freedom than the simulated annealing method used in earlier versions of AUTODOCK, and that the Lamarckian genetic algorithm is the most efficient, reliable, and successful of the three. The empirical free energy function was calibrated using a set of 30 structurally known protein)ligand complexes with experimentally determined binding constants. Linear regression analysis of the observed binding constants in terms of a wide variety of structure-derived molecular properties was performed. The final model had a residual standard y1 y1 .

/pdf/automated-docking-using-a-lamarckian-genetic-algorithm-and-2t6y95r7fm.pdf

Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function

Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications

Signal transduction is initiated by complex protein-protein interactions between ligands, receptors and kinases, to name only a few. It is now becoming clear that lipid micro-environments on the cell surface -- known as lipid rafts -- also take part in this process. Lipid rafts containing a given set of proteins can change their size and composition in response to intra- or extracellular stimuli. This favours specific protein-protein interactions, resulting in the activation of signalling cascades.

/pdf/lipid-rafts-and-signal-transduction-2pg659jt8g.pdf

Lipid rafts and signal transduction

Optical tweezers use the forces exerted by a strongly focused beam of light to trap and move objects ranging in size from tens of nanometres to tens of micrometres. Since their introduction in 1986, the optical tweezer has become an important tool for research in the fields of biology, physical chemistry and soft condensed matter physics. Recent advances promise to take optical tweezers out of the laboratory and into the mainstream of manufacturing and diagnostics; they may even become consumer products. The next generation of single-beam optical traps offers revolutionary new opportunities for fundamental and applied research.

http://physics.nyu.edu/grierlab/nreview2c/nreview2c.pdf

A revolution in optical manipulation

The adhesion force between the tip of an atomic force microscope cantilever derivatized with avidin and agarose beads functionalized with biotin, desthiobiotin, or iminobiotin was measured Under conditions that allowed only a limited number of molecular pairs to interact, the force required to separate tip and bead was found to be quantized in integer multiples of 160 +/- 20 piconewtons for biotin and 85 +/- 15 piconewtons for iminobiotin The measured force quanta are interpreted as the unbinding forces of individual molecular pairs

https://science.sciencemag.org/content/sci/264/5157/415.full.pdf

Adhesion forces between individual ligand-receptor pairs.

To probe the dynamics and size of lipid rafts in the membrane of living cells, the local diffusion of single membrane proteins was measured. A laser trap was used to confine the motion of a bead bound to a raft protein to a small area (diam ≤ 100 nm) and to measure its local diffusion by high resolution single particle tracking. Using protein constructs with identical ectodomains and different membrane regions and vice versa, we demonstrate that this method provides the viscous damping of the membrane domain in the lipid bilayer. When glycosylphosphatidylinositol (GPI) -anchored and transmembrane proteins are raft-associated, their diffusion becomes independent of the type of membrane anchor and is significantly reduced compared with that of nonraft transmembrane proteins. Cholesterol depletion accelerates the diffusion of raft-associated proteins for transmembrane raft proteins to the level of transmembrane nonraft proteins and for GPI-anchored proteins even further. Raft-associated GPI-anchored proteins were never observed to dissociate from the raft within the measurement intervals of up to 10 min. The measurements agree with lipid rafts being cholesterol-stabilized complexes of 26 ± 13 nm in size diffusing as one entity for minutes.

/pdf/sphingolipid-cholesterol-rafts-diffuse-as-small-entities-in-1mc18vgsil.pdf

Sphingolipid–Cholesterol Rafts Diffuse as Small Entities in the Plasma Membrane of Mammalian Cells

The recognition mechanisms and dissociation pathways of the avidin-biotin complex and of actin monomers in actin filaments were investigated. The unbinding forces of discrete complexes of avidin or streptavidin with biotin analogs are proportional to the enthalpy change of the complex formation but independent of changes in the free energy. This result indicates that the unbinding process is adiabatic and that entropic changes occur after unbinding. On the basis of the measured forces and binding energies, an effective rupture length of 9.5 +/- 1 angstroms was calculated for all biotin-avidin pairs and approximately 1 to 3 angstroms for the actin monomer-monomer interaction. A model for the correlation among binding forces, intermolecular potential, and molecular function is proposed.

https://science.sciencemag.org/content/sci/266/5183/257.full.pdf

Intermolecular forces and energies between ligands and receptors

Flocking birds, fish schools, and insect swarms are familiar examples of collective motion that plays a role in a range of problems, such as spreading of diseases. Models have provided a qualitative understanding of the collective motion, but progress has been hindered by the lack of detailed experimental data. Here we report simultaneous measurements of the positions, velocities, and orientations as a function of time for up to a thousand wild-type Bacillus subtilis bacteria in a colony. The bacteria spontaneously form closely packed dynamic clusters within which they move cooperatively. The number of bacteria in a cluster exhibits a power-law distribution truncated by an exponential tail. The probability of finding clusters with large numbers of bacteria grows markedly as the bacterial density increases. The number of bacteria per unit area exhibits fluctuations far larger than those for populations in thermal equilibrium. Such “giant number fluctuations” have been found in models and in experiments on inert systems but not observed previously in a biological system. Our results demonstrate that bacteria are an excellent system to study the general phenomenon of collective motion.

/pdf/collective-motion-and-density-fluctuations-in-bacterial-4ri7rd2nb6.pdf

Ernst-Ludwig Florin

Papers

Adhesion forces between individual ligand-receptor pairs.

Sphingolipid–Cholesterol Rafts Diffuse as Small Entities in the Plasma Membrane of Mammalian Cells

Intermolecular forces and energies between ligands and receptors

Collective motion and density fluctuations in bacterial colonies.

Sensing specific molecular interactions with the atomic force microscope