Propulsion of a molecular machine by asymmetric distribution of reaction products

A simple model for the reaction-driven propulsion of a small device is proposed as a model for (part of) a molecular machine in aqueous media. The motion of the device is driven by an asymmetric distribution of reaction products. The propulsive velocity of the device is calculated as well as the scale of the velocity fluctuations. The effects of hydrodynamic flow as well as a number of different scenarios for the kinetics of the reaction are addressed.     

Exploring the mechanism of flexible biomolecular recognition with single molecule dynamics

Combining a single-molecule study of protein binding with a coarse grained molecular dynamics model including solvent (water molecules) effects, we find that biomolecular recognition is determined by flexibilities in addition to structures. Our single-molecule study shows that binding of CBD (a fragment of Wiskott-Aldrich syndrome protein) to Cdc42 involves bound and loosely bound states, which can be quantitatively explained in our model as a result of binding with large conformational changes. Our model identified certain key residues for binding consistent with mutational experiments. Our study reveals the role of flexibility and a new scenario of dimeric binding between the monomers: first bind and then fold.     

Application of Coarse-Grained (CG) Models to Explore Conformational Pathway of Large-Scale Protein Machines

Protein machines are clusters of protein assemblies that function in order to control the transfer of matter and energy in cells. For a specific protein machine, its working mechanisms are not only determined by the static crystal structures, but also related to the conformational transition dynamics and the corresponding energy profiles. With the rapid development of crystallographic techniques, the spatial scale of resolved structures is reaching up to thousands of residues, and the concomitant conformational changes become more and more complicated, posing a great challenge for computational biology research. Previously, a coarse-grained (CG) model aiming at conformational free energy evaluation was developed and showed excellent ability to reproduce the energy profiles by accurate electrostatic interaction calculations. In this study, we extended the application of the CG model to a series of large-scale protein machine systems. The spike protein trimer of SARS-CoV-2, ATP citrate lyase (ACLY) tetramer, and P4-ATPases systems were carefully studied and discussed as examples. It is indicated that the CG model is effective to depict the energy profiles of the conformational pathway between two endpoint structures, especially for large-scale systems. Both the energy change and energy barrier between endpoint structures provide reasonable mechanism explanations for the associated biological processes, including the opening of receptor binding domain (RBD) of spike protein, the phospholipid transportation of P4-ATPase, and the loop translocation of ACLY. Taken together, the CG model provides a suitable alternative in mechanistic studies related to conformational change in large-scale protein machines.     

Solvent-induced DNA conformational transition

Modified water models with scaled charges are used to investigate solvent polarity effects on DNA structure. Several intensive molecular dynamics simulations of the DNA EcoRI dodecamer d(CGCGAATTCGCG) in different model solvents are performed. When the polarity of the solvent molecule decreases, from overpolarized to less polarized, DNA experiences the conformational transitions of constrained-->B form-->(A-B)mix-->A form. We demonstrate that one important cause of these structure changes is the competition between hydration and direct cation coupling to the free oxygen atoms in the phosphate groups on DNA backbones.     

REDUCING OPERATOR-INDUCED MACHINE VIBRATION USING A COMPLEX POLE/ZERO PREFILTER

A systematic prefilter design process for reducing operator-induced rigid body vibrations of rubber tire mounted machines is presented. The contribution of this work is the development of a systematic prefilter design process and interpretation of the results. The class of heavy equipment considered in this work are those machines having rigid body main frame vibrations dominated by linear dynamics. The reduction in machine vibrations is accomplished through the design of prefilters that reduce the machine resonant frequencies from the operator commands. The machine information required for the design process includes the bandwidth of the electro-hydraulic (E/H) valves and rigid body resonant frequencies of the machine mainframe. The prespecified performance in the design process is the desired attenuation of machine resonant frequencies which is related to the acceptable level of machine vibration. The design methodology has been applied to a telescopic boom lift to illustrate the procedure and the effectiveness of the design.     

Differential temperature Carnot heat analysis shows that computing machines are thermodynamically irreversible

We perform a differential temperature Carnot analysis of the changes in energy and entropy (degrees of freedom) associated with an ideal classical computing machine. Assuming that Carnot’s maximum efficiency law is as equally applicable to a computing machine as to a mechanical machine, we find that useful computation is necessarily dissipative and thermodynamically irreversible. In addition, we find that copying or cloning of information is as dissipative as the original process employed to create the information (through a computation) in the first place. We prove minimum heat dissipation kT ln 2 per output calculation bit, where T is the thermodynamic temperature of unavoidable by-product bits (i.e. not the output calculation bits) rather than a generally assumed ‘surrounding environment’ temperature. Overall, this places computers into the same category as conventional machines, obeying the second law of thermodynamics and always operating below 100% efficiency, such that a perpetual calculating machine cannot exist.     

电磁流体表面推进机理与效果分析

电磁流体表面推进是在推进单元周围的导电流体中(海水、等离子体等)激励出电磁体积力,并利用电磁体积力的反作用力达到推进的目的. 基于电磁场和流体力学的基本控制方程,采用有限体积法对电磁流体表面推进的效果进行了数值模拟研究,分析了在不同姿态(攻角)和不同电磁体积力的作用下,航行器周围流场结构的变化规律和推力的变化特点.研究结果表明:沿航行器表面分布的电磁体积力可以有效地改变流体边界层的结构,并能向流体边界层传输动量与能量,从而使航行器获得所需的推力.流体对航行器的黏性阻力和压差阻力的影响随作用参数的增大而减弱 关键词： 表面推进 航行器 推进单元 电磁体积力     

Stiffness and conformations of molecular bottle-brushes strongly adsorbed on a flat surface

A theory of the conformational behavior and analysis of the persistence length of molecular bottle-brushes strongly adsorbed on a flat surface in a good solvent is presented. For long enough side chains we have shown that the adsorption of a small fraction of side chains already leads to significant increase of the stiffness and drastic conformational changes of the brush in comparison with the 3D case. For a symmetrical distribution of the adsorbed side chains with respect to the backbone, the equilibrium conformation of the brush is close to a rod-like one due to the very large stiffness of the molecule. Under certain conditions the excluded-volume interactions of the side chains of an asymmetrical brush can lead to its bending or twisting in spiral. The obtained results are in good agreement with computer simulations. Received 13 April 2000 and Received in final form 18 August 2000     

Molecular association of pentanols in n-heptane II: Viscosities as a function of temperature covering low concentration range

Viscosities of binary mixtures of isomeric pentanols in n-heptane at various mole fractions, F (F = 0.025 to 0.600) have been measured in the low temperature range (T = 233 to 293 K) with an automatic viscometer operating in a closed system. The temperature dependence of viscosity has been found to follow a simple relation, thereby allowing for the calculation of E_v, the activation energy for viscous flow. The latter is very sensitive to changes in molecular associates, especially at low concentrations. The results show that at low concentrations small multimers dominate for both 1-pentanol and 2-pentanol. At high concentrations, while the former may associate to give large linear multimers; the latter may result in the formation of large cyclic multimers with a low dipole moment. For 3-pentanol and tert-pentanol, small multimers are likely to dominate at low concentrations and there is a change in the dominating multimers from a linear type to a cyclic one, with increasing concentration in the limit F<0.100. However, at high concentrations, dipolar multimers dominate for 3-pentanol while large cyclic multimers of nondipolar type may be significant for tert-pentanol. These conclusions are consistent with those results obtained from Kerr effect, ¹³C NMR relaxation and the Kirkwood g-factor of the same or related alcohols.     

Spectroscopic and Electrochemical Studies on the Interaction of Carmoisine Food Additive with Native Calf Thymus DNA

ABSTRACT

In this work, for the first time interaction between a carmoisine food additive and native calf thymus DNA was monitored using UV-Vis absorption, fluorescence, and circular dichroism (CD) spectroscopy, as well as cyclic voltammetry and viscosity measurements. It can be concluded that carmoisine could interact with DNA via a groove-binding mode as evidenced by a hyperchromic effect of absorption spectra, increases in the fluorescence quenching effect of DNA, certain induced CD spectral changes, and relatively small changes in the viscosity of DNA. The binding constants (K_b) for the carmoisine with DNA was estimated to be 6.2 × 10⁴ M^?1 through spectroscopic titrations. The cyclic voltammetry method showed that both anodic and cathodic peak currents of carmoisine decreased upon addition of the DNA. Circular dichroism spectra indicated that there are certain detectable conformational changes such as conversion from B-like to A-like in the DNA double helix when carmoisine was added.     

Tryptophan-Tryptophan Energy Transfer and Classification of Tryptophan Residues in Proteins Using a Therapeutic Monoclonal Antibody as a Model

Intrinsic tryptophan (Trp) fluorescence is often used to determine conformational changes of proteins. The fluorescence of multi-Trp proteins is generally assumed to be additive. This assumption usually holds well if Trp residues are situated at long distances from each other in the absence of any excited state reactions involving these residues and therefore when energy transfer does not occur. Here, we experimentally demonstrate energy transfer among Trp residues and support it by a Master Equation kinetic model applied to a therapeutic monoclonal antibody (mAb). The mAbs are one of the most studied and important biologics for the pharmaceutical industry, and they contain many Trp residues in close proximity. Understanding mAb fluorescence is critical for interpreting fluorescence data and protein-structure relationships. We propose that Trp residues could be categorized into three types of emitters in the mAbs. Experimentally, we categorize them according to solvent accessibility based on dependence of their fluorescence lifetime on the external quencher concentration and their emission wavelength. Theoretically, we categorize with molecular dynamics simulations according to their solvent accessibility. This method of combinatorial mapping of fluorescence characteristics can be utilized to illuminate structural aspects as well as make comparisons of drug formulations for these pharmaceutical proteins.     

A novel Monte Carlo scheme for the rapid equilibration of atomistic model polymer systems of precisely defined molecular architecture

Two novel connectivity-altering atomistic Monte Carlo moves are presented for the fast equilibration of condensed phases of long-chain systems with a variety of chain architectures. With the new moves, isotropic or oriented melts of linear or long-chain branched polymers, dense brushes of terminally grafted macromolecules, and cyclic peptides can be simulated. Results concerning the structural, conformational, and volumetric properties of linear, monodisperse polyethylene melts, simulated with a new united-atom molecular model, are in excellent agreement with experimental data.     

丝素蛋白在甲醇-水混合溶剂中构象变化的光谱学研究

应用圆二色谱、内源荧光和外源荧光探针研究了丝素蛋白在甲醇-水混合溶剂中的构象变化及机理。结果显示,在浓度低于30%(V/V)的甲醇-水混合溶剂中,处于无规卷曲状态的丝素蛋白可以通过疏水相互作用形成小的疏水区域,随着甲醇浓度的增加,丝素蛋白发生由无规卷曲向β-折叠的构象转变,削弱了疏水侧链的相互作用。分析表明,丝素蛋白的构象变化与溶剂体系的微观结构密切相关,其稳定性主要由肽键单元与混合溶剂中的分子簇之间的相互作用决定。低浓度的甲醇-水混合溶剂保持水固有的氢键结构,对丝素蛋白肽键单元的溶剂化和丝素蛋白构象的影响较小,而随着甲醇浓度的增加,溶剂结构出现由四面体结构的水分子簇向链状结构的甲醇分子簇的转变,丝素蛋白通过形成分子内氢键减少肽键单元与溶剂分子的接触,从而引发丝素蛋白的构象转变。     

约束条件下胶球间排空力的研究

用MonteCarlo方法对处于两平行硬板约束下三个浓度的大小胶球系统进行了模拟,通过对大胶球表面小胶球密度的统计,由密度积分公式获得了大胶球所受的排空力.研究结果显示,因为平行硬板的存在或当改变两平行硬板的距离时,同浓度下,排空力在硬板距离小的时候最明显;三个浓度中,浓度高的,排空力受硬板距离影响最大;有硬板约束比无该约束的时候,排空力效果更显著.     

Refractive indices and thermo-optical properties of dye laser solvents

By measuring the wavelength tuning of a distributed feedback dye laser, solvent refractive-index changes as small as 0.0002 may be determined. This technique hence allows precise measurement of refractive-index dependence on temperature (dn/dT) and therefore enables the thermo-optical properties of solvents used in dye lasers to be assessed. In addition to single component solvents, the thermo-optical properties of solvent mixtures and additives are reported here. The refractive-index change with temperature (dn/dT) is related to solvent density change with temperature (dq/dT) through molecular polarizability.     

MLIMCL：基于机器学习的隐式溶剂蒙特卡罗方法

对于分子结构的优化和预测,蒙特卡罗(MC)是很重要的计算工具. 当溶剂效应被显式的考虑时,由于水分子和电离子的自由度很大,蒙特卡罗方法变得非常昂贵. 相对而言,基于隐式溶剂的蒙特卡罗方法可以通过对溶剂效应平均场的近似来大大降低计算成本,同时还能保持目标分子在原子水平上的细节. 目前两种最流行的隐式溶剂模型是泊松-波兹曼模型和通用化波恩模型. 通用化波恩模型是泊松-波兹曼模型的近似,但在模拟计算时间上要快得多. 本文通过结合两种隐式溶剂模型在准确性和效率方面的优势,开发了一种基于机器学习的隐式溶剂蒙特卡罗方法. 具体而言,蒙特卡罗方法通过机器学习既保留了泊松-波兹曼模型的精度,又达到了通用化波恩模型的速度,从而能快速准确地获取模拟计算中每一步的静电溶解自由能. 本文采用苯-水系统和蛋白质-水系统来验证我们的蒙特卡罗方法. 实验证明蒙特卡罗方法在分子结构优化和预测的速度和准确性方面具有很大优势.     

Using filtering effects to identify objects

Reflecting signals off of targets is a method widely used to locate objects, but the reflected signal also contains information that can be used to identify the object. In radar or sonar, the signal amplitudes used are small enough that only linear effects are present, so we can consider the effect of the target on the signal as a linear filter. Using the known effects of linear filters on chaotic signals, we can create a reference that allows us to match a particular target to a particular reflected signal. Furthermore, if some parts of this "filter" vary only slowly as the aspect angle of the object changes, we can produce a reference that averages out the parts that are highly angle dependent so that one reference can be used to identify the target over a range of angles.     

Role of fluctuations in ligand binding cooperativity of membrane receptors

Signal transduction upon binding of a ligand to a membrane protein can occur not only via allosteric conformational changes but also through fluctuations. We report a numerical study on the influence of conformational fluctuations on the cooperativity of a binding reaction in a simple model of an integral membrane receptor consisting of transmembrane helices. We find that small fluctuations lateral as well as perpendicular to the membrane can increase the cooperativity, with the former more dominant. Moreover, too much fluctuation induces negative cooperativity. Proteins with fewer than four helices do not show positive cooperativity under any circumstances. This behavior is rather robust, and independent of the receptor topology or ligand size. Fluctuations measured in all-atom molecular dynamics simulations of a G-protein coupled receptor fall within the predicted region of maximum cooperativity.     

Computer-aided molecular modeling of polymers. III. enthalpy of polymerization as a measure of stability

A formalism of computational chemistry methods is presented to estimate the stability of vinyl polymers. This approach takes into account changes in electronic energy upon polymerization using quantum mechanical methods and contributions of the conformational energetics of the polymerized state using a molecular mechanics force field. A work term, ΔV, based upon the molecular volume difference between the monomer and the reactant, is shown to be negligible. For 10 structurally diverse vinyl polymers, the sum of the electronic and conformational energy differences between reactant and monomer states, AEp, has a high linear correlation with corresponding measured enthalpies of polymerization, ΔHp. The linear regression least square fit is ΔHp = 0.89 AEp-13.39. Errors due to possible contributions to AHp not included in the formalism reported here are probably small and/or relatively constant over the set of polymers studied. If this were not the case, a linear correlation between AHp and AEp, with a slope near 1, would not be observed. Most likely the intercept of-13.39 kcal/mol is due to the choice of the quantum mechanical method used, MNDO. Overall, the formalism presented here seems a reliable means of predicting relative polymerization stability, in advance of synthesis, for a structurally congeneric set of polymers.