Kinetic Rate Constant Prediction Supports the Conformational Selection Mechanism of Protein Binding

The prediction of protein-protein kinetic rate constants provides a fundamental test of our understanding of molecular recognition, and will play an important role in the modeling of complex biological systems. In this paper, a feature selection and regression algorithm is applied to mine a large set of molecular descriptors and construct simple models for association and dissociation rate constants using empirical data. Using separate test data for validation, the predicted rate constants can be combined to calculate binding affinity with accuracy matching that of state of the art empirical free energy functions. The models show that the rate of association is linearly related to the proportion of unbound proteins in the bound conformational ensemble relative to the unbound conformational ensemble, indicating that the binding partners must adopt a geometry near to that of the bound prior to binding. Mirroring the conformational selection and population shift mechanism of protein binding, the models provide a strong separate line of evidence for the preponderance of this mechanism in protein-protein binding, complementing structural and theoretical studies

Optimisation of material properties for the modelling of large deformation manufacturing processes using a finite element model of the Gleeble compression test

The finite element modelling of manufacturing processes often requires a large amount of large plastic strain flow stress data in order to represent the material of interest over a wide range of temperatures and strain rates. Compression data generated using a Gleeble thermo-mechanical simulator is difficult to interpret due to the complex temperature and strain fields, which exist within the specimen during the test. In this study, a non-linear optimisation process is presented, which includes a finite element model of the compression process to accurately determine the constants of a five-parameter Norton–Hoff material model. The optimisation process is first verified using a reduced three-parameter model and then the full five-parameter model using a known set of constants to produce the target data, from which the errors are assessed. Following this, the optimisation is performed using experimental target data starting from a set of constants derived from the test data using an initial least-squares fit and also an arbitrary starting point within the parameter space. The results of these tests yield coefficients differing by a maximum of less than 10% and significantly improve the representation of the flow stress of the material

Two-photon fluorescence isotropic-single-objective microscopy

International audienceTwo-photon excitation provides efficient optical sectioning in three-dimensional fluorescence microscopy, independently of a confocal detection. In two-photon laser-scanning microscopy, the image resolution is governed by the volume of the excitation light spot, which is obtained by focusing the incident laser beam through the objective lens of the microscope. The light spot being strongly elongated along the optical axis, the axial resolution is much lower than the transverse one. In this Letter we show that it is possible to strongly reduce the axial size of the excitation spot by shaping the incident beam and using a mirror in place of a standard glass slide to support the sample. Provided that the contribution of sidelobes can be removed through deconvolution procedures, this approach should allow us to achieve similar axial and lateral resolution

Isotropic Single Objective (ISO) microscopy : Theory and Experiment

International audienceIsotropic single-objective (ISO) microscopy is a recently proposed imaging technique that can theoretically exhibit the same axial and transverse resolutions as 4Pi microscopy while using a classical single-objective confocal microscope. This achievement is obtained by placing the sample on a mirror and shaping the illumination beam so that the interference of the incident and mirror-reflected fields yields a quasi-spherical spot. In this work, we model the image formation in the ISO fluorescence microscope and simulate its point spread function. Then, we describe the experimental implementation and discuss its practical difficulties

Evolution entre 2007 et 2009 de la résistance des Entérobactéries et de Pseudomonas aeruginosa à la ciprofloxacine, en fonction de la consommation de fluoroquinolones au CHU d'Angers

National audienc

Frequency shifts of photoassociative spectra of ultracold metastable Helium atoms : a new measurement of the s-wave scattering length

We observe light-induced frequency shifts in one-color photoassociative spectra of magnetically trapped $^4$He$^*$ atoms in the metastable $2^3S_1$ state. A pair of ultracold spin-polarized $2^3S_1$ helium atoms is excited into a molecular bound state in the purely long range $0_u^+$ potential connected to the $2^3S_1 - 2^3P_0$ asymptote. The shift arises from the optical coupling of the molecular excited bound state with the scattering states and the bound states of two colliding $2^3S_1$ atoms. We measure the frequency-shifts for several ro-vibrational levels in the $0^+_u$ potential and find a linear dependence on the photoassociation laser intensity. Comparison with a theoretical analysis provides a good indication for the s-wave scattering length $a$ of the quintet ($^5\Sigma_g^+$) potential, $a=7.2\pm 0.6$ nm, which is significantly lower than most previous results obtained by non-spectroscopic methods.Comment: 7 pages, 4 figure