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MOTIVATION The in silico prediction of potential interactions between drugs and target proteins is of core importance for the identification of new drugs or novel targets for existing drugs. However, only a tiny portion of all drug-target pairs in current datasets are experimentally validated interactions. This motivates the need for developing(More)
Today's energy functions are not able yet to distinguish reliably between correct and almost correct protein models. Improving these near-native models is currently a major bottle-neck in homology modeling or experimental structure determination at low resolution. Increasingly accurate energy functions are required to complete the "last mile of the protein(More)
Leptin is a key factor in the regulation of food intake and is an important factor in the pathophysiology of obesity. However, more than a decade after the discovery of leptin in mouse, information regarding leptin in any nonmammalian species is still scant. We report the identification of duplicate leptin genes in common carp (Cyprinus carpio). The unique(More)
We describe duplicate leptin genes in zebrafish (Danio rerio) that share merely 24% amino acid identity with each other and only 18% with human leptin. We were also able to retrieve a second leptin gene in medaka (Oryzias latipes). The presence of duplicate leptin genes in these two distantly related teleosts suggests that duplicate leptin genes are a(More)
State-of-the-art methods based on CNS and CYANA were used to recalculate the nuclear magnetic resonance (NMR) solution structures of 500+ proteins for which coordinates and NMR restraints are available from the Protein Data Bank. Curated restraints were obtained from the BioMagResBank FRED database. Although the original NMR structures were determined by(More)
We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampling. The latter allows the evaluation of(More)
The ultimate goal of protein modeling is to predict a structure from its sequence with an accuracy that is comparable to the best results achieved experimentally. This would allow users to safely use rapidly generated in silico protein models in all the contexts where today only experimental structures provide a solid basis: structure-based drug design,(More)
Nuclear Overhauser effect (NOE) data are an indispensable source of structural information in biomolecular structure determination by NMR spectroscopy. The number and type of experimental restraints used in the structure calculation and the RMS deviation of the restraints are usually reported. We present a new method for quantifying the information(More)
Translation termination is accomplished by proteins of the Class I release factor family (RF) that recognize stop codons and catalyze the ribosomal release of the newly synthesized peptide. Bacteria have two canonical RFs: RF1 recognizes UAA and UAG, RF2 recognizes UAA and UGA. Despite that these two release factor proteins are sufficient for de facto(More)
Phosphoribosylpyrophosphate synthetases (PRSs) catalyze the first step of nucleotide synthesis. Nucleotides are central to cell function, being the building blocks of nucleic acids and serving as cofactors in cellular signaling and metabolism. With this in mind, it is remarkable that mutations in phosphoribosylpyrophosphate synthetase 1 (PRPS1), which is(More)