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Molodenskiy, D.

Publications and source records attributed to Molodenskiy, D..

2 recordsLinked to original sources

3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modelling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank.

bioinformatics↗

Autism associated SHANK3 missense point mutations impact conformational fluctuations and protein turnover at synapses

Members of the SH3- and ankyrin-rich repeat (SHANK) protein family are considered as master scaffolds of the post-synaptic density of glutamatergic synapses. Several missense mutations within the canonical SHANK3 isoform have been proposed as causative for the development of autism spectrum disorders (ASDs). However, there is a surprising paucity of data linking missense mutation-induced changes in protein structure and dynamics to the occurrence of ASD-related synaptic phenotypes. In this work, we focus on two ASD-associated point mutations, both located within the same domain of SHANK3. In a proof-of-principle study we demonstrate that both mutant proteins show indeed distinct changes in secondary and tertiary structure as well as higher conformational fluctuations. Local and surprisingly also distal structural disturbances of protein folding result in altered synaptic targeting and changes of protein turnover at synaptic sites.

neuroscience↗