Schrödinger

About: Schrödinger is a based out in . It is known for research contribution in the topics: Sputtering & Ion. The organization has 1621 authors who have published 2200 publications receiving 81554 citations.

IDSite: An accurate approach to predict P450-mediated drug metabolism.

Abstract: Accurate prediction of drug metabolism is crucial for drug design. Since a large majority of drugs metabolism involves P450 enzymes, we herein describe a computational approach, IDSite, to predict P450-mediated drug metabolism. To model induced-fit effects, IDSite samples the conformational space with flexible docking in Glide followed by two refinement stages using the Protein Local Optimization Program (PLOP). Sites of metabolism (SOMs) are predicted according to a physical-based score that evaluates the potential of atoms to react with the catalytic iron center. As a preliminary test, we present in this paper the prediction of hydroxylation and O-dealkylation sites mediated by CYP2D6 using two different models: a physical-based simulation model, and a modification of this model in which a small number of parameters are fit to a training set. Without fitting any parameters to experimental data, the Physical IDSite scoring recovers 83% of the experimental observations for 56 compounds with a very low false positive rate. With only 4 fitted parameters, the Fitted IDSite was trained with the subset of 36 compounds and successfully applied to the other 20 compounds, recovering 94% of the experimental observations with high sensitivity and specificity for both sets.

Chapter 6 - Wear Models for Multiphase Materials and Synergistic Effects in Polymeric Hybrid Composites

Abstract: This chapter presents some of the existing approaches for describing mathematically the friction and wear behaviour of multi-component systems. The relationship between the size of the reinforcing phase and the asperity size plays an important role in friction and wear phenomena. Depending on this parameter, different types of wear behaviour can occur. The abrasive wear of particle-reinforced polymer composites can be described by a simple additive equation based on a series model. The apparent filler wear rate in the composite is higher than that measured for the same material in sheet form and this increase is highly dependent on the type of particle-surface treatment. If these composites are, however, subjected to sliding wear against smooth steel counterparts, the simple rule-of-mixtures description does not apply anymore, due to a higher complexity of the wear mechanisms. From investigations on the unlubricated friction and wear of unidirectionally oriented fibre reinforced polymers (FRP) sliding against carbon steel, the following results were obtained: (1) The law of mixture for the friction coefficient of FRP was deduced, and the validity of this law was assured by the experimental results. (2) Carbon-FRP gave a small specific wear rate and a low friction coefficient. By contrast, glass-FRP provided a large specific wear rate and a high friction coefficient. (3) A model was proposed in which the wear of FRP proceeds by wear-thinning of the fibre with subsequent breakdown of the fibre and by peeling-off of the fibre from the matrix. Using this model, an experimental equation for the wear of FRP was deduced. Further, work concerning the tribological behaviour of hybrid composites has led to the following conclusions: (1) The steady-state wear rates of hybrid composites sliding against stainless steel often lie considerably below the values linearly interpolated between those of the single-fibre composites. Thus, wear synergism is exhibited by the hybrid composites. (2) Fibre orientation affects a composite's wear behaviour, but both the extent of its significance and the optimum orientation for wear resistance depend on the composite's composition. (3) Using the best wear results achieved with monolithic fibre composites, i.e. with carbon fibres oriented in-plane and parallel to the sliding direction, or with aramid fibres in normal orientation, would lead to a model composite with a 3D-hybrid structure, which is supposed to have optimum wear resistance. (4) Approaching this model by producing 2D-hybrid composites shows synergistic effects between different fibre materials and directions chosen. (5) A mathematical, semi-empirical model is suggested that allows one to describe these hybrid effects by (a) starting from a rule-of-mixture prediction on the wear resistance of the hybrid composite, and (b) subtracting a reduction term of the wear rate, resulting from the interactive protection against wear of one component by the other. If the hybrid efficiency factor is negative, the wear of the hybrid composite is, on the other hand, greater than that predicted by the rule-of-mixtures approach.

On the Cauchy Problem for the Korteweg-de Vries Equation with Steplike Finite-Gap Initial Data II. Perturbations with Finite Moments

Abstract: We solve the Cauchy problem for the Korteweg-de Vries equation with steplike quasi-periodic, finite-gap initial conditions under the assumption that the perturbations have a given number of finite derivatives with finite moments.

Rapid prototyping of optical components for surface plasmon polaritons.

Abstract: Advanced femtosecond laser technology allows the fabrication of arbitrary 2D and 3D dielectric micro- and nanoscale structures by two-photon polymerization (2PP). In this paper, we present first investigations on excitation of surface plasmon polaritons (SPPs) on dielectric 2D structures fabricated on metal surfaces with this technology. Straight and curved line- and dot- structures built of the negative-tone photoresist ORMOCER (organically modified ceramic) are investigated by plasmon leakage radiation microscopy. Polarization dependent excitation efficiencies and focusing of SPPs are investigated.