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1.
We propose a novel stochastic method to generate paths conditioned to start in an initial state and end in a given final state during a certain time t(f). These paths are weighted with a probability given by the overdamped Langevin dynamics. We show that these paths can be exactly generated by a non-local stochastic differential equation. In the limit of short times, we show that this complicated non-solvable equation can be simplified into an approximate local stochastic differential equation. For longer times, the paths generated by this approximate equation do not satisfy the correct statistics, but this can be corrected by an adequate reweighting of the trajectories. In all cases, the paths are statistically independent and provide a representative sample of transition paths. The method is illustrated on the one-dimensional quartic oscillator.  相似文献   

2.
Gelation occurred at a concentration of 0.3% curdlan solution at room temperature (25 °C). The curdlan showed a Newtonian behavior at 0.1%, but plastic behavior above 0.2% even at a temperature of 38 °C. The dynamic modulus remained at a constant value with an increase of temperature up to 40 °C., which was estimated to be a transition temperature, then it decreased rapidly with an increase of temperature until 55 °C; however, it increased gradually with a further increase of temperature. The dynamic viscoelasticity of curdlan solution remained at very low values on addition of urea (4 M) and decreased with increasing temperature. The optical rotation of curdlan (0.1%) increased with a decrease of temperature.Possible modes of intra- and intermolecular hydrogen bonding within and between curdlan molecules were proposed. A hydrophobic interaction might take place at high temperatures (>55 °C), the mode of which was also proposed.  相似文献   

3.
A method is suggested to determine valid and authentic values of thermodynamic stability parameters of proteins from their heat-induced conformational transition curves. We show (a) that the estimate of ΔHm van, the enthalpy change on denaturation at Tm, the midpoint of denaturation, is significantly less than ΔHm cal, the value obtained by the calorimetric measurements, if the analysis of the conformational transition curve uses the conventional method which assumes a linear temperature-dependence of the pre- and post-transition baselines; and (b) that there exists an excellent agreement between ΔHm van and ΔHm cal values of proteins, if the analysis of thermal denaturation curves assumes that the temperature-dependence of pre- and post-transition baselines is described by a parabolic function. The latter analysis is supported by our observations that the temperaturedependencies of the absorption and circular dichroism properties of protein groups are indeed nonlinear. It is observed that the estimate of ΔCp, the constant-pressure heat capacity change is independent of the model used to describe the temperaturedependence of the pre- and post-transition baselines. An important conclusion is that for proteins which exhibit a two-state character, all stability parameters are measured with the same error as that observed with a calorimeter.  相似文献   

4.
5.
We describe an algorithm that explores potential energy surfaces (PES) and finds approximate reaction paths and transition states. A few (≈6) evolving atomic configurations ("climbers") start near a local minimum M1 of the PES. The climbers seek a shallow ascent, low energy, path toward a saddle point S12, cross over to another valley of the PES, and climb down to a new minimum M2 that was not known beforehand. Climbers use both energy and energy derivatives to make individual decisions, and they use relative fitness to make team-based decisions. In sufficiently long runs, they keep exploring and may go through a sequence M1-S12-M2-S23-M3 ... of minima and saddle points without revisiting any of the critical points. We report results on eight small test systems that highlight advantages and disadvantages of the method. We also investigated the PES of Li(8), Al(7)(+), Ag(7), and Ag(2)NH(3) to illustrate potential applications of this new method.  相似文献   

6.
Computational studies of dynamics in complex systems require means for generating reactive trajectories with minimum knowledge about the processes of interest. Here, we introduce a method for generating transition paths when an existing one is not already available. Starting from biased paths obtained from steered molecular dynamics, we use a Monte Carlo procedure in the space of whole trajectories to shift gradually to sampling an ensemble of unbiased paths. Application to basin-to-basin hopping in a two-dimensional model system and nucleotide-flipping by a DNA repair protein demonstrates that the method can efficiently yield unbiased reactive trajectories even when the initial steered dynamics differ significantly. The relation of the method to others and the physical basis for its success are discussed.  相似文献   

7.
Low concentrations of alcohols have proven to be able to enlarge the stability curve of globular proteins, by decreasing the cold denaturation temperature and increasing the hot denaturation temperature [S. R. Martin, V. Esposito, P. De Los Rios, A. Pastore and P. A. Temussi, J. Am. Chem. Soc., 2008, 130, 9963-9970]. In order to try to explain these data, I have considered that: (1) an aqueous 2 M MeOH solution can be treated as a uniform liquid, constituted by water molecules, whose density, above the temperature of maximum density, has the same values of neat water, simply shifted by 2 °C toward lower temperatures, whereas, below the temperature of maximum density, it decreases to a slightly lesser extent than the density of neat water; (2) the ΔE(a)(2 M MeOH) quantity, a balance between intra-protein energetic attractions and those with the surrounding solvent molecules, both water and methanol, assumes a constant positive value. These physically-based assumptions, when inserted into the theoretical model developed to rationalize the occurrence of cold denaturation in neat water [G. Graziano, Phys. Chem. Chem. Phys., 2010, 12, 14245-14252], reproduce in a qualitatively correct manner the effect of low concentrations of alcohols.  相似文献   

8.
A general survey is carried out on the theoretical grounds for methods of spin, luminescence and M?ssbauer labels, as well as their application in the study of protein intramolecular dynamics. When combined, these methods allow the protein dynamics to be investigated within a wide range of correlation times (tau c = 10(2) - 10(-10) s) and amplitudes. The purposeful application of the methods to various proteins at different temperatures (30-330 K), water content, substrate addition, etc., revealed a number of dynamical processes and conformational transitions in proteins. The experiments indicated correlations between the local segmental mobility of protein globules in a nanosecond temporal scale and biochemical reactions, such as long-distance electron transfer, hydrolysis and photoreactions. The biophysical labelling methods results were analysed together with the data on dynamics obtained using complementary physico-chemical methods and theoretical calculations. Special emphasis is given to recent results on proteins from thermophylic micro-organisms. The mechanisms of protein intramolecular dynamics and their role in the stability and functions of proteins and enzymes are discussed.  相似文献   

9.
10.
Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase β, are used as case studies to identify the critical residues responsible for their open-closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions.  相似文献   

11.
This paper introduces a widely accessible and straightforward technique for fabricating membrane protein arrays. This technique employs topographically patterned agarose gels to deliver various membrane preparations to glass substrates in a rapid and parallel fashion. It can fabricate more than 30 identical copies of a membrane protein array while requiring only femtomoles of protein. Taking advantage of on-stamp preconcentration, it is able to pattern arrays of multilayered membrane spots with more than 20-fold increased content of membrane proteins compared to existing methods.  相似文献   

12.
A highly constrained amino acid has been introduced in the turn region of a beta-helix to increase the conformational stability of the native fold for nanotechnological purposes. The influence of this specific amino acid replacement in the final organization of beta-helix motifs has been evaluated by combining ab initio first-principles calculations on model systems and molecular dynamics simulations of entire peptide segments. The former methodology, which has been applied to a sequence containing three amino acids, has been used to develop adjusted templates. Calculations indicated that 1-amino-2,2-diphenylcyclopropanecarboxylic acid, a constrained cyclopropane analogue of phenylalanine, exhibits a strong tendency to form and promote folded conformations. On the other hand, molecular dynamics simulations are employed to probe the ability of such a synthetic amino acid to enhance the conformational stability of the beta-helix motif, which is the first requirement for further protein nanoengineering. A highly regular segment from a naturally occurring beta-helix protein was selected as a potential nanoconstruct module. Simulations of wild type and mutated segments revealed that the ability of the phenylalanine analogue to nucleate turn conformations enhances the conformational stability of the beta-helix motif in isolated peptide segments.  相似文献   

13.
The evolution of our physics-based computational methods for determining protein conformation without the introduction of secondary-structure predictions, homology modeling, threading, or fragment coupling is described. Initial use of a hard-sphere potential captured much of the structural properties of polypeptide chains, and subsequent more refined force fields, together with efficient methods of global optimization provide indications that progress is being made toward an understanding of the interresidue interactions that underlie protein folding.  相似文献   

14.
Current resolved structures of GPCRs and G protein complexes provided important insights into G protein activation. However, the binding or dissociation of GPCRs with G protein is instantaneous and highly dynamic in the intracellular environment. The conformational dynamic of G protein still needs to be addressed. In this study, we applied19 F solution NMR spectroscopy to monitor the conformational changes of G protein upon interact with detergent mimicking membrane and receptor. Our results sho...  相似文献   

15.
The conformational transition of horse heart cytochrome c induced by bromopyrogal red (BPR) in very low concentration has been firstly investigated by dynamic spectroelectrochemical technique, both at the BPR adsorbed platinum gauze electrode and at a bare platinum gauze electrode in a solution containing BPR. The effect of BPR on the structure of cytochrome c was studied by UV-visible and Fourier transform IR spectroscopy. The unfolded cytochrome c behaves simply as an electron transfer protein with a formal potential of −142 mV vs. a normal hydrogen electrode. The difference between the formal potentials of the native and unfolded cytochrome c is coupled to a difference in conformational energy of the two states of about 40 kJ mol−1, which agrees well with the result reported. The stability and slow refolding of the unfolded cytochrome c are discussed.  相似文献   

16.
17.
In this brief paper, we review recent and significant results obtained in our laboratory by dielectric spectroscopy (DS). This is a multi purpose and very sensitive approach to investigate structural features of biological systems. DS at radiofrequencies is particularly powerful in the study of structural and conformational properties of proteins. We report on results obtained on three well-known proteins: lysozyme, cytochrome-c and metmyoglobin, which represent very useful models for folding/unfolding studies. The influence of pH and temperature as well as presence of trehalose as a co-solvent, was determined by estimation of the effective hydrodynamic radius and electric dipole moment of the protein in solution. In particular, trehalose was shown to affect the alkaline transition of cytochrome. Conformational effects on the three above-mentioned proteins were observed in a temperature range near the physiological ones. Dynamical properties of lysozyme in mixtures water-glycerol are also discussed. Parallel measurements of photon correlation spectroscopy (PCS) and DS indicated that both translational and rotational diffusive behavior are coherent with the Debye-Stokes-Einstein hydrodynamic model.  相似文献   

18.
19.
Electron transport (ETp) across bacteriorhodopsin (bR), a natural proton pump protein, in the solid state (dry) monolayer configuration, was studied as a function of temperature. Transport changes from thermally activated at T > 200 K to temperature independent at <130 K, similar to what we have observed earlier for BSA and apo-azurin. The relatively large activation energy and high temperature stability leads to conditions where bR transports remarkably high current densities above room temperature. Severing the chemical bond between the protein and the retinal polyene only slightly affected the main electron transport via bR. Another thermally activated transport path opens upon retinal oxime production, instead of or in addition to the natural retinal. Transport through either or both of these paths occurs on a background of a general temperature-independent transport. These results lead us to propose a generalized mechanism for ETp across proteins, in which tunneling and hopping coexist and dominate in different temperature regimes.  相似文献   

20.
Conformational dynamics and observed equilibrium constants for ligand binding of the adenine-specific riboswitch (add-A riboswitch) in the absence of Mg(2+) and presence of various concentrations of poly-ethylene glycol having an average molecular weight of 200 indicated that 54.2 water molecules were released from P2 and P3 stem regions of the add-A riboswitch during conformational transition upon the binding of 2-aminopurine, an analog of the natural ligand adenine.  相似文献   

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