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We introduce a new algorithm, IRECS (Iterative REduction of Conformational Space), for identifying ensembles of most probable side-chain conformations for homology modeling. On the basis of a given rotamer library, IRECS ranks all side-chain rotamers of a protein according to the probability with which each side chain adopts the respective rotamer(More)
T-cell receptors (TCR) play an important role in the adaptive immune system as they recognize pathogen- or cancer-based epitopes and thus initiate the cell-mediated immune response. Therefore there exists a growing interest in the optimization of TCRs for medical purposes like adoptive T-cell therapy. However, the molecular mechanisms behind T-cell(More)
Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the question how this sixth base is recognized by cellular proteins. In contrast to the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5-methylcytosine containing substrates with(More)
The inhibitor telaprevir (VX-950) of the hepatitis C virus (HCV) protease NS3-4A has been tested in a recent phase 1b clinical trial in patients infected with HCV genotype 1. This trial revealed residue mutations that confer varying degrees of drug resistance. In particular, two protease positions with the mutations V36A/G/L/M and T54A/S were associated(More)
Using molecular dynamics, we study the unbinding of ATP in F(1)-ATPase from its tight binding state to its weak binding state. The calculations are made feasible through use of interpolated atomic structures from Wang and Oster [Nature 1998, 396: 279-282]. These structures are applied to atoms distant from the catalytic site. The forces from these distant(More)
Steroids are important pharmaceutically active compounds. In contrast to the liver drug-metabolising cytochrome P450s, which metabolise a variety of substrates, steroid hydroxylases generally display a rather narrow substrate specificity. It is therefore a challenging goal to change their regio- and stereoselectivity. CYP106A2 is one of only a few bacterial(More)
MOTIVATION The binding of endogenous antigenic peptides to MHC class I molecules is an important step during the immunologic response of a host against a pathogen. Thus, various sequence- and structure-based prediction methods have been proposed for this purpose. The sequence-based methods are computationally efficient, but are hampered by the need of(More)
The cytochrome P450 monooxygenase CYP106A2 from Bacillus megaterium ATCC 13368 catalyzes hydroxylations of a variety of 3-oxo-Δ(4) -steroids such as progesterone and deoxycorticosterone (DOC), mainly in the 15β-position. We combined a high-throughput screening and a rational approach for identifying new substrates of CYP106A2. The diterpene resin acid(More)
Experimental screening of large sets of peptides with respect to their MHC binding capabilities is still very demanding due to the large number of possible peptide sequences and the extensive polymorphism of the MHC proteins. Therefore, there is significant interest in the development of computational methods for predicting the binding capability of(More)
Molecular docking programs play an important role in drug development and many well-established methods exist. However, there are two situations for which the performance of most approaches is still not satisfactory, namely inclusion of receptor flexibility and docking of large, flexible ligands like peptides. In this publication a new approach is presented(More)