154 research outputs found
Accounting for thermodynamic non-ideality in the Guinier region of small-angle scattering data of proteins
Hydrodynamic studies of the solution properties of proteins and other biological macromolecules are often hard to interpret when the sample is present at a reasonably concentrated solution. The reason for this is that solutions exhibit deviations from ideal behaviour which is manifested as thermodynamic non-ideality. The range of concentrations at which this behaviour typically is exhibited is as low as 1-2Â mg/ml, well within the range of concentrations used for their analysis by techniques such as small-angle scattering. Here we discuss thermodynamic non-ideality used previously used in the context of light scattering and sedimentation equilibrium analytical ultracentrifugation and apply it to the Guinier region of small-angle scattering data. The results show that there is a complementarity between the radially averaged structure factor derived from small-angle X-ray scattering/small-angle neutron scattering studies and the second virial coefficient derived from sedimentation equilibrium analytical ultracentrifugation experiments
Lattice Boltzmann simulations of soft matter systems
This article concerns numerical simulations of the dynamics of particles
immersed in a continuum solvent. As prototypical systems, we consider colloidal
dispersions of spherical particles and solutions of uncharged polymers. After a
brief explanation of the concept of hydrodynamic interactions, we give a
general overview over the various simulation methods that have been developed
to cope with the resulting computational problems. We then focus on the
approach we have developed, which couples a system of particles to a lattice
Boltzmann model representing the solvent degrees of freedom. The standard D3Q19
lattice Boltzmann model is derived and explained in depth, followed by a
detailed discussion of complementary methods for the coupling of solvent and
solute. Colloidal dispersions are best described in terms of extended particles
with appropriate boundary conditions at the surfaces, while particles with
internal degrees of freedom are easier to simulate as an arrangement of mass
points with frictional coupling to the solvent. In both cases, particular care
has been taken to simulate thermal fluctuations in a consistent way. The
usefulness of this methodology is illustrated by studies from our own research,
where the dynamics of colloidal and polymeric systems has been investigated in
both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures,
76 page
Implications from a Network-Based Topological Analysis of Ubiquitin Unfolding Simulations
BACKGROUND: The architectural organization of protein structures has been the focus of intense research since it can hopefully lead to an understanding of how proteins fold. In earlier works we had attempted to identify the inherent structural organization in proteins through a study of protein topology. We obtained a modular partitioning of protein structures with the modules correlating well with experimental evidence of early folding units or "foldons". Residues that connect different modules were shown to be those that were protected during the transition phase of folding. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we follow the topological path of ubiquitin through molecular dynamics unfolding simulations. We observed that the use of recurrence quantification analysis (RQA) could lead to the identification of the transition state during unfolding. Additionally, our earlier contention that the modules uncovered through our graph partitioning approach correlated well with early folding units was vindicated through our simulations. Moreover, residues identified from native structure as connector hubs and which had been shown to be those that were protected during the transition phase of folding were indeed more stable (less flexible) well beyond the transition state. Further analysis of the topological pathway suggests that the all pairs shortest path in a protein is minimized during folding. CONCLUSIONS: We observed that treating a protein native structure as a network by having amino acid residues as nodes and the non-covalent interactions among them as links allows for the rationalization of many aspects of the folding process. The possibility to derive this information directly from 3D structure opens the way to the prediction of important residues in proteins, while the confirmation of the minimization of APSP for folding allows for the establishment of a potentially useful proxy for kinetic optimality in the validation of sequence-structure predictions
The Energy Landscapes of Repeat-Containing Proteins: Topology, Cooperativity, and the Folding Funnels of One-Dimensional Architectures
Repeat-proteins are made up of near repetitions of 20â to 40âamino acid stretches. These polypeptides usually fold up into non-globular, elongated architectures that are stabilized by the interactions within each repeat and those between adjacent repeats, but that lack contacts between residues distant in sequence. The inherent symmetries both in primary sequence and three-dimensional structure are reflected in a folding landscape that may be analyzed as a quasiâone-dimensional problem. We present a general description of repeat-protein energy landscapes based on a formal Ising-like treatment of the elementary interaction energetics in and between foldons, whose collective ensemble are treated as spin variables. The overall folding properties of a complete âdomainâ (the stability and cooperativity of the repeating array) can be derived from this microscopic description. The one-dimensional nature of the model implies there are simple relations for the experimental observables: folding free-energy (ÎGwater) and the cooperativity of denaturation (m-value), which do not ordinarily apply for globular proteins. We show how the parameters for the âcoarse-grainedâ description in terms of foldon spin variables can be extracted from more detailed folding simulations on perfectly funneled landscapes. To illustrate the ideas, we present a case-study of a family of tetratricopeptide (TPR) repeat proteins and quantitatively relate the results to the experimentally observed folding transitions. Based on the dramatic effect that single point mutations exert on the experimentally observed folding behavior, we speculate that natural repeat proteins are âpoisedâ at particular ratios of inter- and intra-element interaction energetics that allow them to readily undergo structural transitions in physiologically relevant conditions, which may be intrinsically related to their biological functions
Translational diffusion coefficient of wormlike regular three-arm stars
Effects of chain stiffness on the translational diffusion coefficient Dor (effective) hydrodynamic radius RH (â D[â1]) are examined theoretically for the regular three-arm star polymers on the basis of the KratkyâPorod (KP) wormlike chain model. The ratio gH of RHof the regular KP three-arm star touched-bead model to that of the KP linear one, both having the same (reduced) total contour lengthL and (reduced) bead diameter db, is numerically evaluated on the basis of the Kirkwood formula and/or the KirkwoodâRiseman (KR) hydrodynamic equation. From an examination of the behavior of the Kirkwood value gH(K) and the KR one gH(KR) of gH as a function of L and db, it is found that both of gH(K) and gH(KR) are insensitive to change in L irrespective of the value of db and that gH(KR) is slightly larger than gH(K) in the ranges of L and db investigated. An empirical interpolation formula is constructed for gH(K), which reproduces the asymptotic valuesâ3/(2â2-1) (=0.947) in the random-coil limit and 1 in the thin-rod limit
Theoretical Calculation of Diffusion Coefficient and Viscosity of Star Polymers in Solution
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