We consider the dynamics of a charged active Brownian particle in three dimensions subjected to an external magnetic field. We show that, in the presence of a field gradient, a macroscopic flux ...emerges from a flux-free system and the density distribution becomes inhomogeneous. The flux is induced by the gradient of the magnetic field only and does not require additional symmetry breaking such as density or potential gradients. This stands in marked contrast to similar phenomena in condensed matter such as the classical Hall effect. We further demonstrate that passive tracer particles can be used to measure the essential effects caused by the Lorentz force on the active particle bath, and we discuss under which conditions this diffusive Hall-like effect might be observed experimentally.
We compare the efficiency of three stochastic optimization methods, simulated annealing, parallel tempering and stochastic tunneling to locate the global minima of complex and rugged potential energy ...surfaces arising from atomistic models for receptor–ligand docking. The stochastic tunneling method proves to be the most efficient generic approach for atomistic receptor–ligand docking in the rigid ligand – rigid receptor approximation.
The stochastic tunneling technique is applied to screen a database of chemical compounds to the active site of dihydrofolate reductase for lead candidates in the receptor–ligand docking problem. ...Using an atomistic force field we consider the ligand’s internal rotational degrees of freedom. It is shown that the natural ligand (methotrexate) scores best among 10
000 randomly chosen compounds. We analyze the top scoring compounds to identify hot-spots of the receptor. We mutate the amino acids that are responsible for the hot-spots of the receptor and verify that its specificity is lost upon modification.
An important contribution to today's computer-aided drug design is the automated screening of large compound databases against structurally resolved protein receptors targets. The introduction of ...ligand flexibility has, by now, become a standardized procedure. In contrast, a general approach to treat target degrees of freedom is still to be found, a consequence of the extreme increase of computational complexity, which comes along with the relaxation of protein degrees of freedom. In this chapter, we discuss in some detail both benefits and present limitations of target flexibility for high-throughput in silico database screens. Among the benefits are an improved diversity of binding modes, which allows one to identify a wider class of drug candidates. The limitations are related to a diminishing docking accuracy and an increased number of false hits. Using the thymidine kinase receptor and ten known inhibitors as an example, we describe in detail how target flexibility was implemented and how it affected the screening performance.
We report on results for the in silico screening of a database of 10
000 flexible compounds against various crystal structures of the thymidine kinase enzyme complexed with 10 known inhibitors. We ...provide a quantitative analysis of the deviations in the ranking of the inhibitors depending on the choice of receptor conformation and imply that the inclusion of side-chain degrees of freedom to the receptor would significantly improve the predictive power of the screening approach. We suggest a consensus score that, in the case of several known native structures of the receptor, enables the evaluation of scoring functions without the requirement of explicit receptor-flexibility.
We investigate the impact of receptor flexibility with the all-atom FlexScreen docking approach using the thymidine kinase (TK) receptor as a model system. We study the screening performance when ...selected side chains of the target are treated in a continously flexible fashion in a screen of a database of 10000 compounds, which contains ten known substrates for the TK receptor. While the binding modes of the known substrates are not significantly affected as a function of receptor flexibility the mean binding energies of the database screen initially drop rapidly with increasing receptor flexibility but saturate when the number of target degrees of freedom is increased further. We demonstrate a dramatically increased diversity of the screen as 40% newly selected ligands appear in the top 500 ligands of the screen when receptor flexibility is taken into consideration.
Mixed polymer brushes as functional ultra thin films for surface functionalization have an enormous potential to create a variety of smart, switchable, and multifunctional surfaces and thin films. It ...is shown how computer simulations can contribute to a better understanding of the switching behavior of brushes. Furthermore, it is described how polymer brushes can be used to create surfaces with switchable ultrahydrophobicity and wettability gradients, as well as functional layers for the immobilization of nanoparticles. Applications of these versatile and multifunctional brush coatings are envisioned in many areas including fluid control, microfluidics, and thin film sensors.
Polymer brushes made of one or two linear polymers are a very versatile tools to create functional (active) and switchable surfaces and thin films. The improvement of the understanding of the switching behaviour by computer simulation, the creation of surfaces with switching ultrahydrophobicity and wettability gradients as well as the immobilization of nanoparticles, is demonstrated together with applications in microfluidics and thin film sensors.
Polymer brushes near the crystallization density HE, G.-L; MERLITZ, H; SOMMER, J.-U ...
The European physical journal. E, Soft matter and biological physics,
12/2007, Letnik:
24, Številka:
4
Journal Article
Recenzirano
In this paper, polymer brushes are studied via molecular-dynamics simulations at very high grafting densities, where the crossover between the brush regime and the polymer-crystal regime is taking ...place. This crossover is directly observed with the structure factor and pair-correlation function. With increasing grafting density, this crystallization is progressing from the core layer of the brush towards the surface layer. The same process is analyzed using the lateral fluctuations of the monomers as a signature of their diminishing mobility. Additionally, bond forces and the chain excess free energy indicate a transition from the brush regime to the overstretched regime, which is in agreement with predictions of a modified self-consistent field theory.
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