1,720,962 research outputs found
Dynamic Force Spectroscopy of Molecular Adhesion Bonds
No full textRecent advances in atomic force microscopy, biomembrane force probe experiments, and optical tweezers allow one to measure the response of single molecules to mechanical stress with high precision. Such experiments, due to limited spatial resolution, typically access only one single force value in a continuous force profile that characterizes the molecular response along a reaction coordinate. We develop a theory that allows one to reconstruct force profiles from force spectra obtained from measurements at varying loading rates, without requiring increased resolution. We show that spectra obtained from measurements with different spring constants contain complementary information
Elastic properties of poly(ethylene-glycol) studied by molecular dynamics stretching simulations.
Full text linkUnfolding and elastic properties of single poly(ethylene-glycol) (PEG) polymers were studied by molecular dynamics (MD) simulations. The simulations were performed in close resemblance to recent single molecule force spectroscopy experiments, and thus allowed an interpretation of these experiments at the atomic level. In agreement with these experiments, the water solvent was found to drastically affect the elastic properties of PEG. Our simulations explain this effect in terms of local helical structures which are stabilized through water bridges. Stretching forces of more than 100 pN were required to break these water bridges and thereby to destroy these helical structures
AN02/DNP-hapten unbinding forces studied by molecular dynamics atomic force microscopy simulations.
Full text linkUnbinding forces of a spin-labeled dinitrophenyl (DNP) hapten from the monoclonal antibody AN02 Fab fragment have been studied by molecular dynamics atomic force microscopy (AFM) simulations. In our nanosecond simulations, unbinding was enforced by pulling the hapten molecule out of the binding pocket. From the simulations unbinding forces of the complex have been determined as a function of pulling velocity. Considering activated unbinding and frictional forces, we used a simple model to extrapolate the unbinding forces to the millisecond timescale of single molecule AFM unbinding experiments. For such experiments the simulations suggest an unbinding force of 60±30 pN
Molecular dynamics force probe simulations of antibody/antigen unbinding: Entropic control and non-additivity of unbinding forces.
No full textAbstractUnbinding of a spin-labeled dinitrophenyl (DNP) hapten from the monoclonal antibody AN02 Fab fragment has been studied by force probe molecular dynamics (FPMD) simulations. In our nanosecond simulations, unbinding was enforced by pulling the hapten molecule out of the binding pocket. Detailed inspection of the FPMD trajectories revealed a large heterogeneity of enforced unbinding pathways and a correspondingly large flexibility of the binding pocket region, which exhibited induced fit motions. Principal component analyses were used to estimate the resulting entropic contribution of ∼6 kcal/mol to the AN02/DNP-hapten bond. This large contribution may explain the surprisingly large effect on binding kinetics found for mutation sites that are not directly involved in binding. We propose that such “entropic control” optimizes the binding kinetics of antibodies. Additional FPMD simulations of two point mutants in the light chain, Y33F and I96K, provided further support for a large flexibility of the binding pocket. Unbinding forces were found to be unchanged for these two mutants. Structural analysis of the FPMD simulations suggests that, in contrast to free energies of unbinding, the effect of mutations on unbinding forces is generally nonadditive
’Chair-boat‘ transitions and side groups affect the stiffness of polysaccharides.
Full text linkAtomic force microscopy experiments with individual β-(1,4)-glucose polymers (cellulose) and α-(1,4)-glucose polymers (amylose) have been simulated by molecular dynamics stretching simulations, and force/extension curves were calculated. For forces above 1200 pN, we predict a stiffness of 5100 pN/Å for both polymers. In contrast to β-glucose, α-glucose exhibits increased flexibility in the 300–1200 pN range, which our simulations attribute to conformational 'chair-boat' transitions of the α-glucose monomers. For β-glucose no such transitions were seen. We suggest a mechanism of neighbor inhibition, which should allow the tailoring of elastic properties through modification of inter-monomeric rotational flexibility, e.g., by introducing or removing bulky or charged side groups
Ligand binding: Molecular mechanics calculation of the streptavidin-biotin rupture force.
Full text linkThe force required to rupture the streptavidin-biotin complex was calculated here by computer simulations. The computed force agrees well with that obtained by recent single molecule atomic force microscope experiments. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, additional water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were observed
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
- …
