998 resultados para Library Dynamics


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A wealth of information available from x-ray crystallographic structures of enzyme-ligand complexes makes it possible to study interactions at the molecular level. However, further investigation is needed when i) the binding of the natural substrate must be characterized, because ligands in the stable enzyme-ligand complexes are generally inhibitors or the analogs of substrate and transition state, and when ii) ligand binding is in part poorly characterized. We have investigated these aspects i? the binding of substrate uridyl 3',5'-adenosine (UpA) to ribonuclease A (RNase A). Based on the systematically docked RNase A-UpA complex resulting from our previous study, we have undertaken a molecular dynamics simulation of the complex with solvent molecules. The molecular dynamics trajectories of this complex are analyzed to provide structural explanations for varied experimental observations on the ligand binding at the B2 subsite of ribonuclease A. The present study suggests that B2 subsite stabilization can be effected by different active site groups, depending on the substrate conformation. Thus when adenosine ribose pucker is O4'-endo, Gln69 and Glu111 form hydrogen-bonding contacts with adenine base, and when it is C2'-endo, Asn71 is the only amino acid residue in direct contact with this base. The latter observation is in support of previous mutagenesis and kinetics studies. Possible roles for the solvent molecules in the binding subsites are described. Furthermore, the substrate conformation is also examined along the simulation pathway to see if any conformer has the properties of a transition state. This study has also helped us to recognize that small but concerted changes in the conformation of the substrate can result in substrate geometry favorable for 2',3' cyclization. The identified geometry is suitable for intraligand proton transfer between 2'-hydroxyl and phosphate oxygen atom. The possibility of intraligand proton transfer as suggested previously and the mode of transfer before the formation of cyclic intermediate during transphosphorylation are discussed.

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Valinomycin is a highly flexible cyclic dodecadepsipeptide that transports ions across membranes. Such a flexibility in the conformation is required for its biological function since it has to encounter a variety of environments and liganding state. Exploration of conformational space of this molecule is therefore important and is one of the objectives of the present study that has been carried out by means of high temperature Molecular Dynamics. Further, the stability of the known bracelet-like structure of the uncomplexed valinomycin and the inherent flexibility around this structure has been investigated. The uncomplexed form of valinomycin has been simulated at 75–100 K for 1 ns in order to elucidate the average conformational properties. An alanine-analog of valinomycin has been simulated under identical conditions in order to evaluate the effect of sidechain on the conformational properties, The studies confirm the effect of sidechain on conformational equilibrium.

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We present a generic theory for the dynamics of a stiff filament under tension, in an active medium with orientational correlations, such as a microtubule in contractile actin. In sharp contrast to the case of a passive medium, we find the filament can stiffen, and possibly oscillate or buckle, depending on both the contractile or tensile nature of the activity and the filament-medium anchoring interaction. We also demonstrate a strong violation of the fluctuation-dissipation (FD) relation in the effective dynamics of the filament, including a negative FD ratio. Our approach is also of relevance to the dynamics of axons, and our model equations bear a remarkable formal similarity to those in recent work [Martin P, Hudspeth AJ, Juelicher F (2001) Proc Natl Acad Sci USA 98: 14380-14385] on auditory hair cells. Detailed tests of our predictions can be made by using a single filament in actomyosin extracts or bacterial suspensions.

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Nonlinear optical properties and carrier relaxation dynamics in graphene, suspended in three different solvents, are investigated using femtosecond (80 fs pulses) Z-scan and degenerate pump-probe spectroscopy at 790 nm. The results demonstrate saturable absorption property of graphene with a nonlinear absorption coefficient, beta of (similar to 2-9) x 10(-8) cm/W. Two distinct time scales associated with the relaxation of photoexcited carriers, a fast one in the range of 130-330 fs (related to carrier-carrier scattering) followed by it slower one in 3.5-4.9 ps range (associated with carrier-phonon scattering) are observed. (C) 2009 American Institute of Physics.

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We derive a very general expression of the survival probability and the first passage time distribution for a particle executing Brownian motion in full phase space with an absorbing boundary condition at a point in the position space, which is valid irrespective of the statistical nature of the dynamics. The expression, together with the Jensen's inequality, naturally leads to a lower bound to the actual survival probability and an approximate first passage time distribution. These are expressed in terms of the position-position, velocity-velocity, and position-velocity variances. Knowledge of these variances enables one to compute a lower bound to the survival probability and consequently the first passage distribution function. As examples, we compute these for a Gaussian Markovian process and, in the case of non-Markovian process, with an exponentially decaying friction kernel and also with a power law friction kernel. Our analysis shows that the survival probability decays exponentially at the long time irrespective of the nature of the dynamics with an exponent equal to the transition state rate constant.

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Regular electrical activation waves in cardiac tissue lead to the rhythmic contraction and expansion of the heart that ensures blood supply to the whole body. Irregularities in the propagation of these activation waves can result in cardiac arrhythmias, like ventricular tachycardia (VT) and ventricular fibrillation (VF), which are major causes of death in the industrialised world. Indeed there is growing consensus that spiral or scroll waves of electrical activation in cardiac tissue are associated with VT, whereas, when these waves break to yield spiral- or scroll-wave turbulence, VT develops into life-threatening VF: in the absence of medical intervention, this makes the heart incapable of pumping blood and a patient dies in roughly two-and-a-half minutes after the initiation of VF. Thus studies of spiral- and scroll-wave dynamics in cardiac tissue pose important challenges for in vivo and in vitro experimental studies and for in silico numerical studies of mathematical models for cardiac tissue. A major goal here is to develop low-amplitude defibrillation schemes for the elimination of VT and VF, especially in the presence of inhomogeneities that occur commonly in cardiac tissue. We present a detailed and systematic study of spiral- and scroll-wave turbulence and spatiotemporal chaos in four mathematical models for cardiac tissue, namely, the Panfilov, Luo-Rudy phase 1 (LRI), reduced Priebe-Beuckelmann (RPB) models, and the model of ten Tusscher, Noble, Noble, and Panfilov (TNNP). In particular, we use extensive numerical simulations to elucidate the interaction of spiral and scroll waves in these models with conduction and ionic inhomogeneities; we also examine the suppression of spiral- and scroll-wave turbulence by low-amplitude control pulses. Our central qualitative result is that, in all these models, the dynamics of such spiral waves depends very sensitively on such inhomogeneities. We also study two types of control chemes that have been suggested for the control of spiral turbulence, via low amplitude current pulses, in such mathematical models for cardiac tissue; our investigations here are designed to examine the efficacy of such control schemes in the presence of inhomogeneities. We find that a local pulsing scheme does not suppress spiral turbulence in the presence of inhomogeneities; but a scheme that uses control pulses on a spatially extended mesh is more successful in the elimination of spiral turbulence. We discuss the theoretical and experimental implications of our study that have a direct bearing on defibrillation, the control of life-threatening cardiac arrhythmias such as ventricular fibrillation.

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The dynamics of loop formation by linear polymer chains has been a topic of several theoretical and experimental studies. Formation of loops and their opening are key processes in many important biological processes. Loop formation in flexible chains has been extensively studied by many groups. However, in the more realistic case of semiflexible polymers, not much results are available. In a recent study [K. P. Santo and K. L. Sebastian, Phys. Rev. E 73, 031923 (2006)], we investigated opening dynamics of semiflexible loops in the short chain limit and presented results for opening rates as a function of the length of the chain. We presented an approximate model for a semiflexible polymer in the rod limit based on a semiclassical expansion of the bending energy of the chain. The model provided an easy way to describe the dynamics. In this paper, using this model, we investigate the reverse process, i.e., the loop formation dynamics of a semiflexible polymer chain by describing the process as a diffusion-controlled reaction. We make use of the ``closure approximation'' of Wilemski and Fixman [G. Wilemski and M. Fixman, J. Chem. Phys. 60, 878 (1974)], in which a sink function is used to represent the reaction. We perform a detailed multidimensional analysis of the problem and calculate closing times for a semiflexible chain. We show that for short chains, the loop formation time tau decreases with the contour length of the polymer. But for longer chains, it increases with length obeying a power law and so it has a minimum at an intermediate length. In terms of dimensionless variables, the closing time is found to be given by tau similar to L-n exp(const/L), where n=4.5-6. The minimum loop formation time occurs at a length L-m of about 2.2-2.4. These are, indeed, the results that are physically expected, but a multidimensional analysis leading to these results does not seem to exist in the literature so far.

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The interdependence of the concept of allostery and enzymatic catalysis, and they being guided by conformational mobility is gaining increased prominence. However, to gain a molecular level understanding of llostery and hence of enzymatic catalysis, it is of utter importance that the networks of amino acids participating in allostery be deciphered. Our lab has been exploring the methods of network analysis combined with molecular dynamics simulations to understand allostery at molecular level. Earlier we had outlined methods to obtain communication paths and then to map the rigid/flexible regions of proteins through network parameters like the shortest correlated paths, cliques, and communities. In this article, we advance the methodology to estimate the conformational populations in terms of cliques/communities formed by interactions including the side-chains and then to compute the ligand-induced population shift. Finally, we obtain the free-energy landscape of the protein in equilibrium, characterizing the free-energy minima accessed by the protein complexes. We have chosen human tryptophanyl-tRNA synthetase (hTrpRS), a protein esponsible for charging tryptophan to its cognate tRNA during protein biosynthesis for this investigation. This is a multidomain protein exhibiting excellent allosteric communication. Our approach has provided valuable structural as well as functional insights into the protein. The methodology adopted here is highly generalized to illuminate the linkage between protein structure networks and conformational mobility involved in the allosteric mechanism in any protein with known structure.

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A study of the magnetohydrodynamic system in which a nonmagnetized fluid in a gravitational field is surrounded by a fluid carrying a vertical magnetic field is presented. It is pointed out that this study can throw some light on the fine-structural features of a sunspot. The equilibrium configuration of the field-free fluid is a tapering column ending at an apex. The regions away form the apex can be studied by the slender flux tube approximation. A scheme developed to treat the apex indicates that, just below the apex, the radius of the tapering column opens up with a 3/2 power dependence on the depth below the apex. If the internal pressure of the field-free fluid is increased, the apex rises, and a static equilibrium may not be possible beyond a limit if the magnetic pressure drops quickly above a certain height. The nature of steady-flow solutions beyond this limit is investigated. Under conditions inside a sunspot, a column of field-free gas is found to rise with a velocity of about 100 km/hr. If umbral dots and penumbral grains are interpreted as regions where the field-free gas ultimately emerges, a very natural explanation of most of their observed properties is obtained.

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A model of polymer translocation based on the stochastic dynamics of the number of monomers on one side of a pore-containing surface is formulated in terms of a one-dimensional generalized Langevin equation, in which the random force is assumed to be characterized by long-ranged temporal correlations. The model is introduced to rationalize anomalies in measured and simulated values of the average time of passage through the pore, which in general cannot be satisfactorily accounted for by simple Brownian diffusion mechanisms. Calculations are presented of the mean first passage time for barrier crossing and of the mean square displacement of a monomeric segment, in the limits of strong and weak diffusive bias. The calculations produce estimates of the exponents in various scaling relations that are in satisfactory agreement with available data.

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Inosine 5' monophosphate dehydrogenase (IMPDH II) is a key enzyme involved in the de novo biosynthesis pathway of purine nucleotides and is also considered to be an excellent target for cancer inhibitor design. The conserve R 322 residue (in human) is thought to play some role in the recognition of inhibitor and cofactor through the catalytic D 364 and N 303. The 15 ns simulation and the water dynamics of the three different PDB structures (1B3O, 1NF7, and 1NFB) of human IMPDH by CHARMM force field have clearly indicated the involvement of three conserved water molecules (W-L, W-M, and W-C) in the recognition of catalytic residues (R 322, D 364, and N 303) to inhibitor and cofactor. Both the guanidine nitrogen atoms (NH1 and NH 2) of the R 322 have anchored the di- and mono-nucleotide (cofactor and inhibitor) binding domains via the conserved W-C and W-L water molecules. Another conserved water molecule W-M seems to bridge the two domains including the R 322 and also the W-C and W-L through seven centers H-bonding coordination. The conserved water molecular triad (W-C - W-M - W-L) in the protein complex may thought to play some important role in the recognition of inhibitor and cofactor to the protein through R 322 residue.

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A new form of a multi-step transversal linearization (MTL) method is developed and numerically explored in this study for a numeric-analytical integration of non-linear dynamical systems under deterministic excitations. As with other transversal linearization methods, the present version also requires that the linearized solution manifold transversally intersects the non-linear solution manifold at a chosen set of points or cross-section in the state space. However, a major point of departure of the present method is that it has the flexibility of treating non-linear damping and stiffness terms of the original system as damping and stiffness terms in the transversally linearized system, even though these linearized terms become explicit functions of time. From this perspective, the present development is closely related to the popular practice of tangent-space linearization adopted in finite element (FE) based solutions of non-linear problems in structural dynamics. The only difference is that the MTL method would require construction of transversal system matrices in lieu of the tangent system matrices needed within an FE framework. The resulting time-varying linearized system matrix is then treated as a Lie element using Magnus’ characterization [W. Magnus, On the exponential solution of differential equations for a linear operator, Commun. Pure Appl. Math., VII (1954) 649–673] and the associated fundamental solution matrix (FSM) is obtained through repeated Lie-bracket operations (or nested commutators). An advantage of this approach is that the underlying exponential transformation could preserve certain intrinsic structural properties of the solution of the non-linear problem. Yet another advantage of the transversal linearization lies in the non-unique representation of the linearized vector field – an aspect that has been specifically exploited in this study to enhance the spectral stability of the proposed family of methods and thus contain the temporal propagation of local errors. A simple analysis of the formal orders of accuracy is provided within a finite dimensional framework. Only a limited numerical exploration of the method is presently provided for a couple of popularly known non-linear oscillators, viz. a hardening Duffing oscillator, which has a non-linear stiffness term, and the van der Pol oscillator, which is self-excited and has a non-linear damping term.

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This review examines recent literature on the public library as a creative place and the ways in which socio-cultural impact is being measured in assessments of cultural value. Inputs such as funding and staffing are frequently measured against outputs such as visitor numbers and lending frequencies, but qualitative measures (outcomes and impacts) are minimal in the literature because of the lack of persuasive evaluative frameworks and the difficulty of designing and facilitating the evaluations at local and national levels. Nevertheless, when combined with data about outputs and outcomes, the impact on individuals and their communities can be measured effectively and reported persuasively (Poll 2012, p.124). This contextual review provides an overview of current thinking about public libraries and creative spaces with particular attention paid to the rise of so-called makerspaces and Fab Labs. This includes discussion on the types of creative activities that are occurring in the public library context, and an outline of the rhetoric and reality of the public library as a community space. These outlines are reconsidered in a discussion of the evaluative frameworks that have been employed by libraries in the past, followed by an account of some prominent creative spaces that have been formally evaluated. The existence of creative spaces in public libraries is in a state of constant flux, and the development and redevelopment of evaluative frameworks will ensure that published reports will continue to appear throughout 2015 and beyond. This review provides a brief snapshot of the state of the field as it is in the first quarter of 2015.