论Folding/Unfolding程序转换的能力

本文讨论Burstall与Darlington提出的folding/unfolding系统的程序转换能力,即讨论从一个给定的程序可以推导出什么样的程序。因此,这是正确性与完备性问题的推广。本文证明了可推导性的一个必要条件,并由此得到了该系统提高程序效率的一个界限。该系统的部分正确性和不完备性也均是该条件的推论。

Improvement of Artificial Foldable Wing Models by Mimicking the Unfolding/Folding Mechanism of a Beetle Hind Wing

In an attempt to realize a flapping wing micro-air vehicle with morphing wings, we report on improvements to our previousfoldable artificial hind wing.Multiple hinges, which were implemented to mimic the bending zone of a beetle hind wing, weremade of small composite hinge plates and tiny aluminum rivets.The buck-tails of rivets were flared after the hinge plates wereassembled with the rivets so that the folding/unfolding motions could be completed in less time, and the straight shape of theartificial hind wing could be maintained after fabrication.Folding and unfolding actions were triggered by electrically-activatedShape Memory Alloy (SMA) wires.For wing folding, the actuation characteristics of the SMA wire actuator were modifiedthrough heat treatment.Through a series of flapping tests, we confirmed that the artificial wings did not fold back and arbitrarilyfluctuate during the flapping motion.

Equilibrium folding and unfolding dynamics to reveal detailed free energy landscape of src SH3 protein by magnetic tweezers

Src SH3 protein domain is a typical two-state protein which has been confirmed by research of denaturant-induced unfolding dynamics.Force spectroscopy experiments by optical tweezers and atomic force microscopy have measured the force-dependent unfolding rates with different kinds of pulling geometry.However,the equilibrium folding and unfolding dynamics at constant forces has not been reported.Here,using stable magnetic tweezers,we performed equilibrium folding and unfolding dynamic measurement and force-jump measurement of src SH3 domain with tethering points at its N-and C-termini.From the obtained force-dependent transition rates,a detailed two-state free energy landscape of src SH3 protein is constructed with quantitative information of folding free energy,transition state barrier height and position,which exemplifies the capability of magnetic tweezers to study protein folding and unfolding dynamics.

A network of conformational transitions in an unfolding process of HP-35 revealed by high-temperature MD simulation and a Markov state model

An understanding of protein folding/unfolding processes has important implications for all biological processes, in- eluding protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics （MD） simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational ca- pabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temper- ature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature （500 K） was performed to investigate the unfolding process of a small protein, chicken villin headpiece （HP-35）. To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.

Force-dependent unfolding and folding dynamics of protein alpha-catenin modulation domains

α-catenin is an adhesion protein located at the cadherin-based cell-cell adherens junction.α-catenin cross-linksβ-catenin and actin fiber in the adhesion protein complex,and plays an important role in the formation and modulation of cell-cell adhesion.The central modulation domains can be unfolded to expose binding site of vinculin when stretching force is applied.Here,we studied the force-induced unfolding dynamics ofα-catenin modulation domains under different loading rates from which the unfolding distance of M2 and M3 domains is determined to be 5-7 nm,and an unfolding intermediate state is identified.We also found that the folding process of M1-M3 domains goes through different pathways with cooperativity.

Folding and Unfolding Simulations of a Three-Stranded Beta-Sheet Protein

Understanding the folding processes of a protein into its three-dimensional native structure only with its amino-acid sequence information is a long-standing challenge in modern science. Two- hundred independent folding simulations (starting from non-native conformations) and two- hundred independent unfolding simulations (starting from the folded native structure) are performed using the united-residue force field and Metropolis Monte Carlo algorithm for betanova (three-stranded antiparallel beta-sheet protein). From these extensive computer simulations, two representative folding pathways and two representative unfolding pathways are obtained in the reaction coordinates such as the fraction of native contacts, the radius of gyration, and the root- mean-square deviation. The folding pathways and the unfolding pathways are similar each other. The largest deviation between the folding pathways and the unfolding pathways results from the root-mean-square deviation near the folded native structure. In general, unfolding computer simulations could capture the essentials of folding simulations.

Structure-activity correlationship and folding of recombinant Escherichia coli dihydro folate reductase (DHFR) enzyme through biochemical and biophysical approaches

The design of any antagonist or inhibitor for any enzyme requires the knowledge of structure- function relationship of the protein and the optimum conformational states for maximum and minimum activities. Furthermore, designing of the inhibitors or drugs against an enzyme becomes easier if there is information available about various well characterized intermediate conformation of the molecule. In vivo folding pathway of any recombinant protein is an important parameter for understanding its ability to fold by itself inside the cell, which always dictates the downstream processing for the purification. In the present manuscript we have discussed about the in vivo and in vitro folding, and structure-function relationship of Dihydrofolate reductase enzyme. This is an important enzyme involved in the cell growth and hence inhibition or inactivation of the enzyme may reduce the cell growth. It was observed that the equilibrium unfolding transition of DHFR proceeds through the formation of intermediates having higher exposed surface hydrophobicity, unchanged enzymatic activity and minimum changes in the secondary structural elements. Because of enhanced surface hydrophobicity, and unchanged enzymatic activity, these intermediates could be a nice target for designing drugs against DHFR.

余维三fold-fold-Hopf分岔下簇发振荡及其分类

不同尺度耦合系统存在着广泛的工程背景,通常表现为大幅振荡与微幅振荡交替出现的簇发振荡,其产生机理一直是当前国内外研究的前沿课题之一.传统的几何奇异摄动分析方法仅对时域上的两尺度耦合有效,无法揭示频域上不同尺度之间的相互作用,同时,当前相关研究仅针对余维一fold或Hopf分岔展开.本文针对频域两尺度耦合向量场存在余维三fold-fold-Hopf分岔时的复杂动力特性,基于包含三阶非线性项以内的该分岔向量场的标准型及其普适开折,给出相应的分岔集,从而将双开折参数平面划分为对应于不同行为的子区域.引入慢变周期激励项取代其中一个开折参数,随慢变激励项的变化,会存在两类轨迹访问子区域途径,产生周期Hopf/LPC,Hopf/LPC/Hopf/LPC,fold/LPC/Hopf/Homoclinic和fold/LPC 4种簇发振荡类型.在分析过程中,发现系统轨迹上的真实分岔,往往与理论上的分岔点之间存在着滞后效应,这种滞后效应的滞后时间也会随着激励幅值的增大而延长,因为激励幅值的增大,会导致轨迹沿相应平衡态运动的惯性增大,特别是,当激励幅值增大到一定值后,会导致轨迹沿某平衡态运动并穿越该区域,也即相关分岔效应来不及出现,从而导致振荡形式的改变.本工作表明,对于局部分岔下的快慢效应,通过向量场标准型开折参数的周期扰动,在一定程度可以对该分岔所导致的所有可能的各种簇发进行归类,并得到其相应的产生机制.

Simulation of the thermodynamics of folding and unfolding of the Trp-cage mini-protein TC5b using different combinations of force fields and solvation models

Molecular dynamics simulations based on AMBER force fields(ff96 and ff03) and generalized Born models(igb1 and igb5) have been carried out in order to study folding/unfolding of the Trp-cage mini-protein TC5b.The thermodynamic properties of TC5b were found to be sensitive to the specific version of the solvation model and force field employed.When the ff96/igb5 combination was used,the predicted melting temperature from unfolding simulations was in good agreement with the experimental value of 315 K,but the folding simulation did not converge.The most stable thermodynamic profile in both folding and unfolding simulations was obtained when the ff03/igb5 combination was employed,and the predicted melting temperature was about 345 K,showing over-stabilization of the protein.Simulations using the igb1 version in combination with ff96 or ff03 were difficult to converge within the simulation time limit(50 ns).

Reversible folding/unfolding of small α-helix in explicit solvent investigated by ABEEMσπ/MM

We have performed molecular dynamics simulations on the reversible folding/unfolding of small α-helix(short Ala based peptide Ala5) in explicit water solvent in terms of ABEEMσπ/MM.A dynamics analysis shows that the α-helical turn can be preserved up to a period of about 2 ns at 300 K,which supports the conclusions of Margulis et al.The time trajectory of the root mean square deviation between the heavy atoms of the backbone and the helical reference structure indicate that "helix melting and formation occurs rapidly on a time scale of 0.1 ns at 300 K" is not a felicitous conclusion.We first quantificationally concluded that the helix nucleation can maintain 2 ns,1―1.5 ns and 0.8 ns for Ala5 at 300 K,400 K and 500 K,respectively.Furthermore,increasing temperature dose not alter the pathway of folding/unfolding,but change the rate.An analysis of structures in a "transition-state ensemble" shows that helix-to-coil transitions occurs predominantly through breaking of hydrogen bonds at the helix ends(92%),particularly at the C-terminus(50%).Hydrogen bonds' breaking and formation occurs on a time scale of 0.1 ns.

Mimicking unfolding motion of a beetle hind wing

This paper presents an experimental research aiming to realize an artificial hind wing that can mimic the wing unfolding motion of Allomyrina dichotoma, an insect in coleopteran order. Based on the understanding of working principles of beetle wing folding/unfolding mechanisms, the hind wing unfolding motion is mimicked by a combination of creative ideas and state-of-art artificial muscle actuator. In this work, we devise two types of artificial wings and the successfully demonstrate that they can be unfolded by actuation of shape memory alloy wires to provide actuation force at the wing base and along the leading edge vein. The folding/unfolding mechanisms may provide an insight for portable nano/micro air vehicles with morphing wings.

Structure and interactions in α-crystallin probed through thiol group reactivity

a-Crystallin is the major structural protein of eye lens of vertebrates. In human lens, the ratio of aA-crystallin to aB-crystallin was found to be 3:1. aA-Crystallin contains two cysteine residues at positions 131 and 142, which are at the junction between the a-crystallin domain and the C-terminal tail. We used the accessibility of the thiol groups by Ellman’s reagent (DTNB) as a tool to gain information about the various structural perturbations of hinge region of a-crystallin and during the binding with substrates. In the native condition, the cys-142 though reacted quite fast was not fully exposed. Several reagents were used to see the accessibility of cys-131. Rate constant for cys-131 was increased gradually with increase in the concentration of reagents. The bindings of substrates are affected by the accessibility of thiol indicating that the substrates bind to the hinge region of a-crystallin. By blocking of cys-142, it was observed that the accessibility of one thiol depends on the other thiol, and they are not independent. The hinge region of a-crystallin is very important as substrate binding site and from this study we have got various structural information about that region.

可折叠热塑性复合材料接头的力学性能

开发了一种芳纶纤维增强热塑性树脂复合材料接头,用于海洋管道非开挖穿插修复内衬管的连接。静液压爆破测试结果表明内压作用下的失效模式是管体本身纤维发生断裂,接头处保持完好;拉伸测试结果表明接头拉伸强度高于内衬管本体强度,满足穿插施工要求。分别建立复合材料接头的内压、拉伸和折叠展开分析模型,通过有限元分析预测了内衬管及接头的极限强度、应力应变分布和变化趋势。有限元结果显示内压作用下主要承载结构为环向纤维,最大应变发生在接头与内衬管本体交接的位置。拉伸作用下主要承载结构为轴向纤维,外层热塑性聚氨酯边缘位置由于应力集中导致应变较大,但仍在材料极限弹性应变范围内。折叠展开大变形过程中,最大应变发生在折叠阶段,接头应变与内衬管本体应变相近。研发的管体中间接头制造方便,尺寸与内衬管匹配性好,可以进行连续盘卷、折叠,满足海底管道一次性长距离修复的要求。

一种导弹横向折叠尾翼的设计及仿真

根据某型导弹尾翼折叠展开机构的设计要求,设计了一种横向尾翼折叠展开机构。研究分析尾翼展开运动过程,建立了数学模型,应用ADAMS动力学仿真软件对尾翼在扭簧驱动作用下的展开过程进行了运动分析,并应用ANSYS Workbench有限元分析软件,对导弹发射离箱瞬间的尾翼解锁及尾翼展开到位时的碰撞进行了动力学仿真分析,仿真结果表明,该型折叠机构设计方案满足设计要求。

“一字型”折叠翼展开试验与仿真验证分析

以某"一字型"折叠翼展开机构为研究对象,应用研制的折叠翼展开试验装置,进行了不同转矩下的展开试验,得到了其关键性能参数变化规律。参照"一字型"折叠翼展开机构原理样机的实际几何参数、物理特性及约束条件,在ADAMS中建立其虚拟样机模型,通过仿真分析得到了对应驱动力下折叠翼的运动参数和展开性能参数的变化规律。对比分析仿真与试验结果可知:弹翼能及时展开到位,准确定位、可靠锁定,且展开过程中各部件之间无干涉,满足设计要求。

多普勒天气雷达风场退模糊方法的研究

文章提出了对多普勒天气雷达的风场信息进行预处理的“K 邻域频数法” ,该方法物理统计意义比较明确 ,能够有效地处理风场信息中的“噪声”问题。在此基础上 ,设计了单径向的速度扩展算法 ,并提出了“双径向 双切向”的方法 ,其效果与美国WSR 88D、NSSL和FSL的算法相当。该文还设计了一个界面十分友好的人机交互方法 ,可以达到约 90 %以上的速度扩展正确率 ,是对传统的人机交互方法的极大改进。

航天器柔性充气式密封舱结构技术的发展

综述了国外充气式舱体的发展历程和研究现状,提炼了其质量、体积、空间布局等3项技术优势,总结了充气式舱体的多功能层合材料体系技术、无损折叠设计技术、刚化技术和地面试验验证技术等4项重点研究内容,对该领域的发展趋势进行了展望,并提出我国的应对策略。

中学生空间图形认知能力的发展研究

研究目的旨在考察中学生空间图形的折叠、展开、旋转以及图形推理等能力的发 展特征和发展水平．研究结果表明：（1）总体而言，学生的空间图形心理表征能力随年级 （或年龄）的增长而提高；（2）不同的任务表征能力具有不完全一致的发展曲线．

中学生空间图形认知能力发展的性别差异研究

本研究的目的旨在考察中学生空间图形的折叠、展开、旋转以及图形推理能力发展的性别差异．研究结果表明：在一定的条件下，存在男生优势的显著性差异．然而，在哪个年龄段男生在哪个空间指标上明显优于女生，尚待实验深入研究．

核磁共振波谱研究蛋白质三维结构及功能

文中总结了中国科学技术大学生命科学学院核磁共振波谱实验室十多年来的工作.我们的研究主要集中于研究人和其他真核生物基因表达调控相关蛋白质以及细胞连接处相关蛋白质.在这两个体系中许多蛋白质与人类健康及疾病相关,有的可能是潜在的药物作用靶标.我们主要关注用核磁共振波谱方法研究蛋白质-蛋白质相互作用的结构基础.核磁共振适合研究在接近生理条件下的分子相互作用,特别是适合研究低亲和力的瞬态的复合物.它可以提供蛋白质相互作用界面,复合物结构,以及蛋白质相互识别过程动力学的信息.文中给出了一些例子.我们也研究蛋白质内部动力学,包括皮秒-纳秒时间尺度,与毫秒-微秒时间尺度的动力学.与圆二色谱及荧光光谱结合,核磁共振可以详细表征蛋白质的折叠与去折叠.文中给出的核磁共振应用的最后一个例子是用计算机虚拟筛选,核磁筛选,我们发现了一个人的双功能的磷酸酶的一种新类型的抑制剂,并研究了该抑制剂对细胞功能的影响.这一策略有可能用于早期药物的发现.