Publications (13) View all
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Article: Is an intuitive convergence definition of molecular dynamics simulations solely based on the root mean square deviation possible?
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ABSTRACT: Molecular dynamics is a commonly used technique in computational biology. One key issue of each molecular dynamics simulation is: When does this simulation reach equilibrium state? A widely used way to determine this is the visual and intuitive inspection of root mean square deviation (RMSD) plots of the simulation. Although this technique has been criticized several times, it is still often used. Therefore, we present a study proving that this method is not reliable at all. We conducted a survey with participants from the field in which we illustrated different RMSD plots to scientists in the field of molecular dynamics. These plots were randomized and repeated, using a statistical model and different variants of the plots. We show that there is no mutual consent about the point of equilibrium. The decisions are severely biased by different parameters. Therefore, we conclude that scientists should not discuss the equilibration of a molecular dynamics simulation on the basis of a RMSD plot.Journal of computational biology: a journal of computational molecular cell biology 06/2011; 18(8):997-1005. · 1.69 Impact Factor -
Article: jSimMacs for GROMACS: a Java application for advanced molecular dynamics simulations with remote access capability.
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ABSTRACT: Molecular dynamics (MD) is a technique to simulate movements of molecular structures to understand their functional behavior. GROMACS is a software package primarily developed for biological MD and offers a huge amount of possible options and settings for tailoring the simulations. This makes it powerful but also complicated to handle. We introduce jSimMacs, a Java application for creating molecular dynamics projects in GROMACS. It simplifies the handling of files and options via an intuitive user interface. Users unexperienced in MD can work along prepared lines, while experts may enjoy a significant relief from the tedium of typing and scripting. Furthermore, jSimMacs supports 3D interactivity and the launch of remote projects on other computers accessible via networks. Thus, jSimMacs not only opens GROMACS to a broader public but also eases the burden of performing series of MD runs, as necessary in parameter studies.Journal of Chemical Information and Modeling 10/2009; 49(10):2412-7. · 4.68 Impact Factor -
Article: A critical cross-validation of high throughput structural binding prediction methods for pMHC.
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ABSTRACT: T-cells recognize antigens via their T-cell receptors. The major histocompatibility complex (MHC) binds antigens in a specific way, transports them to the surface and presents the peptides to the TCR. Many in silico approaches have been developed to predict the binding characteristics of potential T-cell epitopes (peptides), with most of them being based solely on the amino acid sequence. We present a structural approach which provides insights into the spatial binding geometry. We combine different tools for side chain substitution (threading), energy minimization, as well as scoring methods for protein/peptide interfaces. The focus of this study is on high data throughput in combination with accurate results. These methods are not meant to predict the accurate binding free energy but to give a certain direction for the classification of peptides into peptides that are potential binders and peptides that definitely do not bind to a given MHC structure. In total we performed approximately 83,000 binding affinity prediction runs to evaluate interactions between peptides and MHCs, using different combinations of tools. Depending on the tools used, the prediction quality ranged from almost random to around 75% of accuracy for correctly predicting a peptide to be either a binder or a non-binder. The prediction quality strongly depends on all three evaluation steps, namely, the threading of the peptide, energy minimization and scoring.Journal of Computer-Aided Molecular Design 03/2009; 23(5):301-7. · 3.39 Impact Factor -
Article: Graphical user interfaces for molecular dynamics-quo vadis?
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ABSTRACT: In the past years an increasing number of graphical user interfaces for Molecular Dynamics (MD) were presented and concomitantly, more and more Molecular Dynamics studies were published. With the easier application of MD software packages the field runs the risk however, of being pervaded with unreliable results. Therefore, possible benefits and caveats have to be carefully balanced. Here we outline in which respects a broader access of MD via graphical user interfaces may help to increase the usability of Molecular Dynamics simulations while maintaining their quality.Bioinformatics and biology insights 01/2009; 3:103-7. -
Article: MH2c: Characterization of major histocompatibility alpha-helices - an information criterion approach
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ABSTRACT: Major histocompatibility proteins share a common overall structure or peptide binding groove. Two binding groove domains, on the same chain for major histocompatibility class I or on two different chains for major histocompatibility class II, contribute to that structure that consists of two alpha-helices ("wall") and a sheet of eight anti-parallel beta strands ("floor"). Apart from the peptide presented in the groove, the major histocompatibility ?-helices play a central role for the interaction with the T cell receptor. This study presents a generalized mathematical approach for the characterization of these helices. We employed polynomials of degree 1 to 7 and splines with 1 to 2 nodes based on polynomials of degree 1 to 7 on the alpha-helices projected on their principal components. We evaluated all models with a corrected Akaike Information Criterion to determine which model represents the ?-helices in the best way without overfitting the data. This method is applicable for both the stationary and the dynamic characterization of alpha-helices. By deriving differential geometric parameters from these models one obtains a reliable method to characterize and compare ?-helices for a broad range of applications.Computer Physics Communications 02/2012; 183(7):1481–1490. · 3.27 Impact Factor
