Fragment-free approach to protein folding using conditional neural fields

Motivation: One of the major bottlenecks with ab initio protein folding is an effective conformation sampling algorithm that can generate native-like conformations quickly. The popular fragment assembly method generates conformations by restricting the local conformations of a protein to short structural fragments in the PDB. This method may limit conformations to a subspace to which the native fold does not belong because (i) a protein with really new fold may contain some structural fragments not in the PDB and (ii) the discrete nature of fragments may prevent them from building a native-like fold. Previously we have developed a conditional random fields (CRF) method for fragment-free protein folding that can sample conformations in a continuous space and demonstrated that this CRF method compares favorably to the popular fragment assembly method. However, the CRF method is still limited by its capability of generating conformations compatible with a sequence

Designing succinct structural alphabets

Motivation: The 3D structure of a protein sequence can be assembled from the substructures corresponding to small segments of this sequence. For each small sequence segment, there are only a few more likely substructures. We call them the ‘structural alphabet’ for this segment. Classical approaches such as ROSETTA used sequence profile and secondary structure information, to predict structural fragments. In contrast, we utilize more structural information, such as solvent accessibility and contact capacity, for finding structural fragments

Assigning a function to a conserved archaeal metallo-β-lactamase from Haloferax volcanii

The metallo-β-lactamase family of enzymes comprises a large group of proteins with diverse functions in the metabolism of the cell. Among others, this superfamily contains proteins which are involved in DNA and RNA metabolism, acting as nucleases in e.g. repair and maturation. Many proteins have been annotated in prokaryotic genomes as being potential metallo-β-lactamases, but very often the function has not been proven. The protein HVO_2763 from Haloferax volcanii is such a potential metallo-β-lactamase. HVO_2763 has sequence similarity to the metallo-β-lactamase tRNase Z, a tRNA 3′ processing endonuclease. Here, we report the characterisation of this metallo-β-lactamase HVO_2763 in the halophilic archaeon Haloferax volcanii. Using different in vitro assays with the recombinant HVO_2763, we could show that the protein does not have tRNA 3′ processing or exonuclease activity. According to transcriptome analyses of the HVO_2763 deletion strain, expression of proteins involved in membrane transport is downregulated in the mutant. Therefore, HVO_2763 might be involved directly or indirectly in membrane transport