@article{ErnstFackeldeyVolkameretal.2019, author = {Ernst, Natalia and Fackeldey, Konstantin and Volkamer, Andrea and Opatz, Oliver and Weber, Marcus}, title = {Computation of temperature-dependent dissociation rates of metastable protein-ligand complexes}, volume = {45}, journal = {Molecular Simulation}, number = {11}, doi = {10.1080/08927022.2019.1610949}, pages = {904 -- 911}, year = {2019}, abstract = {Molecular simulations are often used to analyse the stability of protein-ligand complexes. The stability can be characterised by exit rates or using the exit time approach, i.e. by computing the expected holding time of the complex before its dissociation. However determining exit rates by straightforward molecular dynamics methods can be challenging for stochastic processes in which the exit event occurs very rarely. Finding a low variance procedure for collecting rare event statistics is still an open problem. In this work we discuss a novel method for computing exit rates which uses results of Robust Perron Cluster Analysis (PCCA+). This clustering method gives the possibility to define a fuzzy set by a membership function, which provides additional information of the kind 'the process is being about to leave the set'. Thus, the derived approach is not based on the exit event occurrence and, therefore, is also applicable in case of rare events. The novel method can be used to analyse the temperature effect of protein-ligand systems through the differences in exit rates, and, thus, open up new drug design strategies and therapeutic applications.}, language = {en} } @article{LangVolkamerBehmetal.2018, author = {Lang, Annemarie and Volkamer, Andrea and Behm, Laura and R{\"o}blitz, Susanna and Ehrig, Rainald and Schneider, Marlon and Geris, Lisbet and Wichard, Joerg and Buttgereit, Frank}, title = {In silico Methods - Computational Alternatives to Animal Testing}, volume = {35}, journal = {ALTEX}, number = {1}, doi = {10.14573/altex.1712031}, pages = {126 -- 128}, year = {2018}, abstract = {A seminar and interactive workshop on "In silico Methods - Computational Alternatives to Animal Testing" was held in Berlin, Germany, organized by Annemarie Lang, Frank Butt- gereit and Andrea Volkamer at the Charit{\´e}-Universit{\"a}tsmedizin Berlin, on August 17-18, 2017. During the half-day seminar, the variety and applications of in silico methods as alternatives to animal testing were presented with room for scientific discus- sions with experts from academia, industry and the German fed- eral ministry (Fig. 1). Talks on computational systems biology were followed by detailed information on predictive toxicology in order to display the diversity of in silico methods and the potential to embrace them in current approaches (Hartung and Hoffmann, 2009; Luechtefeld and Hartung, 2017). The follow- ing interactive one-day Design Thinking Workshop was aimed at experts, interested researchers and PhD-students interested in the use of in silico as alternative methods to promote the 3Rs (Fig. 2). Forty participants took part in the seminar while the workshop was restricted to sixteen participants.}, language = {en} }