Understanding how ligands bind to G-protein coupled receptors (GPCRs) provides insights into a myriad of cell processes and is crucial for drug development. Here we extend a hybrid molecular mechanics/coarse-grained (MM/CG) approach applied previously to enzymes to GPCR/ligand complexes. The accuracy of this method for structural predictions is established by comparison with recent atomistic molecular dynamics simulations on the human β2 adrenergic receptor, a member of the GPCRs superfamily. The results obtained with the MM/CG methodology show a good agreement with previous all-atom classical dynamics simulations, in particular in the structural description of the ligand binding site. This approach could be used for high-throughput predictions of ligand poses in a variety of GPCRs.

Context. Local helioseismology has so far relied on semi-analytical methods to compute the spatial sensitivity of wave travel times to perturbations in the solar interior. These methods are cumbersome and lack flexibility. Aims. Here we propose a convenient framework for numerically solving the forward problem of time-distance helioseismology in the frequency domain. The fundamental quantity to be computed is the cross-covariance of the seismic wavefield. Methods. We choose sources of wave excitation that enable us to relate the cross-covariance of the oscillations to the Green's function in a straightforward manner. We illustrate the method by considering the 3D acoustic wave equation in an axisymmetric reference solar model, ignoring the effects of gravity on the waves. The symmetry of the background model around the rotation axis implies that the Green's function can be written as a sum of longitudinal Fourier modes, leading to a set of independent 2D problems. We use a high-order finite-element method to solve the 2D wave equation in frequency space. The computation is 'embarrassingly parallel', with each frequency and each azimuthal order solved independently on a computer cluster. Results. We compute travel-time sensitivity kernels in spherical geometry for flows, sound speed, and density perturbations under the first Born approximation. Convergence tests show that travel times can be computed with a numerical precision better than one millisecond, as required by the most precise travel-time measurements. Conclusions. The method presented here is computationally efficient and will be used to interpret travel-time measurements in order to infer, e.g., the large-scale meridional flow in the solar convection zone. It allows the implementation of (full-waveform) iterative inversions, whereby the axisymmetric background model is updated at each iteration.

The aim of this paper is to present a new model of in vitro cell electropermeabilization, which describes separately the conducting state and the permeable state of the membrane submitted to high voltage pulses. We first derive the model based on the experimental observations and we present the numerical methods to solve the non-linear partial differential equations. We then present numerical simulations that corroborate qualitatively the experimental data dealing with the uptake of propidium iodide (PI) after millipulses. This tends to justify the validity of our modeling. Forthcoming work will be to calibrate the parameters of the model for quantitative description of the uptake.