Energetics of molecular motor proteins: could it pay to take a free ride?

ABSTRACT

Molecular motor proteins are used in biological systems to generate directed motion. They consist of one end that can bind to and then move along a filament. The other end can then bind to a cargo that needs transporting and the motor then pulls it along. Here, we consider the energetics of this process allowing for the friction force exerted by the surrounding fluid, given that the process takes place in a confined geometry. In nature, not all motor/cargo complexes are bound to the filament, many are in solution. Here, we address the question of whether this can be energetically favourable given that the unbound complexes will be transported by the flow generated by those that are bound. A simple theory suggests that this is the case and that there exists an optimal coverage of bound complexes. Simulations of a model of this system that includes all the relevant hydrodynamic effects confirm that the assumptions in the theory are valid so long as the coverage of bound complexes is not too low. Using realistic values for the parameters involved yields an optimal coverage that is plausible for the biological systems involved.     

Motor proteins transporting cargos

Processive motor proteins such as kinesin and myosin-V are enzymes that use the energy of ATP hydrolysis to travel along polar cytoskeletal filaments. One of the functions of these proteins is the transport of vesicles and protein complexes that are linked to the light chains of the motors. Modeling the light chain by a linear elastic spring, and using the two-state model for one- and two-headed molecular motors, we study the influence of thermal fluctuations of the cargo on the motion of the motor-cargo complex. We solve numerically the Fokker-Planck equations of motor motion, and find that the mean velocity of the motor-cargo complex decreases monotonously as the spring becomes softer. This effect is due to the random force of thermal fluctuations of the cargo disrupting the operation of the motor. Increasing the size (thus, the friction coefficient) of the cargo also decreases the velocity. Surprisingly, we find that for a given size of the cargo, the velocity has a maximum for a certain friction of the motor. We explain this effect by the interplay between the characteristic length of thermal fluctuations of the cargo on a spring, the motor diffusion length, and the filament period. Our results may be relevant for the interpretation of single-molecule experiments with molecular motors (bead assays), where the motor motion is observed by tracking of a bead attached to the motor.     

Determination of paeonol in rat plasma by high-performance liquid chromatography and its application to pharmacokinetic studies following oral administration of Moutan cortex decoction

Quantification of paeonol, the principal bioactive component of Moutan cortex, in rat plasma following oral administration of Moutan cortex decoction was achieved by using a simple and sensitive high-performance liquid chromatographic method. The calibration curves for paeonol were linear in both the low (25-200 ng/mL) and the high concentration range (200-4000 ng/mL) with r(2) values of 0.9928 and 0.9993, respectively. The coefficients of variation of intra- and inter-day assays were 14.36, 6.52, 1.76, 1.25, 5.36, 3.30 and 1.42% and 12.70, 1.19, 2.98, 1.91, 1.75, 1.78 and 0.96% at concentrations of 25, 50, 100, 200, 500, 1000 and 2000 ng/mL, respectively. The recoveries of paeonol from rat plasma were found to be 101.9, 104.5, 105.4 and 101.2% for concentrations of 50, 500, 1000 and 2000 ng/mL, respectively. The paeonol plasma concentrations were fitted to two-compartment model with fi rst order absorption. The mean terminal half-lives (t(1/2)) of paeonol was 80.9 min.     

基于模糊切换增益调节的燃气流量滑模控制

将模糊控制方法与滑模控制方法相结合,针对燃气流量调节伺服系统设计一种基于模糊切换增益调节的滑模控制器,固冲发动机流量调节伺服控制系统的不确定部分通过滑模控制器来补偿,从而可实现固冲发动机流量调节伺服系统的鲁棒控制。使用matlab对固冲发动机流量调节伺服系统进行建模仿真并与单纯使用滑模控制方法进行比较,仿真结果表明基于模糊切换增益调节的固冲发动机模糊滑模控制系统具有较好的给定适应性和抗干扰性,采用该控制方案能有效的抑制系统随机干扰对控制系统的不利影响,控制效果优于纯滑模控制方法,消弱了控制信号的抖振,为提高固冲发动机流量调节控制系统的动态性能奠定基础。     

Cover Picture: Freely Suspended Actin Cortex Models on Arrays of Microfabricated Pillars (ChemPhysChem 8/2003)

The cover picture shows the first demonstration of a biomimetic model of the cellular actin cortex. The actin filamental network imaged as a fluorescent micrograph (orange) is suspended on top of an array of microfabricated silicon pillars, schematically drawn in light blue. The actin network is obtained by polymerising actin filaments from a template provided by gold‐capped pillars. Subsequently adding filamin as actin‐crosslinking protein causes the formation of the ordered network within minutes. Find out more in the article by Spatz and co‐workers on pages 872–877.     

Raman Spectroscopy of Galactosemic Rat Lens Crystalline: Correlation of Microscopic Changes of Lens Proteins at Molecular Levels with Gross Cataractous Alteration

Near‐Infrared Fourier trans form (near‐IR FT) Raman spectros copy has been used to study the structural changes of lens proteins both in cortex and nucleus of galactosemic rat lenses. It was found that tyrosine doublet ratio of Raman bands, I₈₃₂/I₈₅₅, in creased more rapidly in the cortex than in the nucleus during a 5‐week period of galactose feeding, i.e., from 0.86 to 1.1 for the cortex and 0.88 to 0.92 for the nucleus. The ratio obtained for lens nucleus suggests that a lower ratio of less than 1 does not necessarily reflect the apparent transparent state of lens morphology. More over our results for the in crease of tyrosine doubletratio with the extent of cataract formation in galactosemic lens appear to indicate that there is more hydration in crystallins of the cortex than the nucleus since the in creased ratio of tyro sine doublet has been shown to be due to the hydrogen‐bond formation of hydroxyl groups in various tyrosines of proteins with water. The tryptophan band ratio at 880 cm^?1 and 757 cm^? (I₈₈₀/I₇₅₇) under went a precipitous de crease in the cortex and a rather gradual de crease in the nucleus, suggesting buried tryptophan residues become more exposed in the cortex than in the nucleus during galactose‐induced cataractogenesis. Based on the changes of the two ratios, I₈₃₂/I₈₅₅ and I₈₈₀/I₇₅₇, the change of lens protein environment induced by galactosemic feeding appeared to take place in the cortex first, which was consistent with the observation that the development of an opaque lens be gins in the cortex. While no sulfhydryl (‐SH) signal was detected, there was a slow in crease of disulfide (‐S‐S‐) signal in the cortex of galactose‐fed lenses as compared to control lenses with out galactose. This suggested that a loss of lens glutathione occurred early and oxidation of cysteines in crystallins started in the first week, i.e., be fore the onset of cortical cataract. In contrast, for nucleus of galactosemic lenses the signal of the‐SH group was detected and yet the ‐S‐S‐signal of crystallins could not be found. In this study, we have conclusively demonstrated using Raman vibrational band shift that galactosemic cataract be gins in the cortex, and that the lens cortex suffers more structural alteration in crystallins than the nucleus.     

煤间接液化研究进展

报道了中国科学院山西煤炭化学研究所“七五”期间在煤间接液化研究方面的进展，包括煤基合成气合成发动机燃料及合成气制低碳燃料醇技术的研究开发￣［１］。其中煤基合成气合成发动机燃料已完成８０～１００ｔ／ａ中间试验，燃料油收率达１００ｇ／ｍ￣３（ＣＯ＋Ｈ＿２），汽油辛烷值（马达法）达８０，尾气热值达１２５４ｋＪ／ｍ￣３。合成气制低碳燃料醇技术研究开发已完成升级模式，在燃料醇组成中，甲醇占７１～７７％，异丁醇１２～１５％，时空产率为０．２１～０．２５Ｌａｌｃ／Ｌｃａｔ·ｈ．参考文献６篇。     

Direct observation of a target cell of the leaf-closing factor by using novel fluorescence-labeled phyllanthurinolactone

We report the synthesis of the fluorescence-labeled probe 2 based on phyllanthurinolactone 1, which is a leaf-closing substance of Phyllanthus urinaria L. Bioorganic studies using probe 2 showed leaf-closing activity at 1 × 10⁻⁵ M, which was one-hundredth of that of the natural product 1. The fluorescence study using 2 revealed that the target cell for 1 is a motor cell and suggested that some receptors for 1 exist on the plasma membrane of the motor cell as with leaf-opening substances.     

Dihydropyrazole and dihydropyrrole structures based design of Kif15 inhibitors as novel therapeutic agents for cancer

Mitotic Kinesin motors, Eg5 and Kif15, have recently emerged as good targets for cancer as they play an inevitable role during mitosis. But, most of the Eg5 inhibitors were found ineffective when the cancer cells develop resistance to them by escalating the expression of Kif15 as alternative to Eg5. Therefore, the drugs that target Kif15 became necessary to be used either as a single or in combination with Eg5 inhibitors. The present study used 39 dihydropyrazole and 13 dihydropyrrole derivatives that were having in vitro inhibitory potential against kinesin motors to develop a common pharmacophore hypothesis AHRR and atom-based QSAR model. The model was used for virtual screening of ZINC database and the resultant hits were docked against Kif15. The four drug candidates with high docking score were examined for their activity and pharmacokinetic behaviour. Based on the results these drugs could be considered as lead candidates in further drug development for cancer.     

Deformation in cooperative molecular motors

We implement a model to represent the effect of the deformation of the backbone of a system of motor proteins while sliding on a track filament. This model incorporates a nearest neighbor interaction term among the motors for the deformation energy. Correlations induced by this term result in increased motor force for inter-particle distances small compared to the ratchet period. Received 20 February 2001 and Received in final form 31 May 2001