@article {159715, title = {Using protein blocks to build custom fragment libraries from protein structures.}, journal = {Biochimie}, year = {2025}, month = {2025 Aug 13}, abstract = {

The remarkable structural diversity of modern proteins reflects millions of years of evolution, during which sequence space has expanded while many structural features remain conserved. This conservation is evident not only among homologous proteins but also in the recurrence of supersecondary motifs across unrelated proteins, underscoring the abundance and robustness of these structural units. Here, we present a novel pipeline for generating customized protein fragment libraries using protein blocks (PBs)-a structural alphabet that encodes local backbone conformations. Our method efficiently extracts structurally similar fragments from a curated, non-redundant protein structure database by converting three-dimensional structures into one-dimensional PB sequences. By integrating predicted PB sequences with the PB-ALIGN and PB-kPRED tools, our approach identifies relevant fragments independently of sequence homology. Fragment quality is further assessed using a new scoring function that combines secondary structure similarity and PB alignment metrics. The resulting libraries contain fragments of at least seven PBs (11 amino acid residues), covering over 70 \% of the local backbone structure. Our results demonstrate that PBs enable efficient mining of high-quality structural fragments from diverse protein spaces, including proteins with disordered regions. The pipeline is accessible as an online tool (PB-Frag, http://pbpred-us2b.univ-nantes.fr/pbfrag).

}, issn = {1638-6183}, doi = {10.1016/j.biochi.2025.08.011}, author = {Dhingra, Surbhi and T{\'e}letch{\'e}a, St{\'e}phane and Sowdhamini, Ramanathan and Sanejouand, Yves-Henri and de Brevern, Alexandre G and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard} } @article {130540, title = {Influence of pH on indole-dependent heterodimeric interactions between Anopheles gambiae odorant-binding proteins OBP1 and OBP4.}, journal = {Int J Biol Macromol}, year = {2023}, month = {2023 Jun 15}, pages = {125422}, abstract = {

Insect Odorant Binding Proteins (OBPs) constitute important components of their olfactory apparatus, as they are essential for odor recognition. OBPs undergo conformational changes upon pH change, altering their interactions with odorants. Moreover, they can form heterodimers with novel binding characteristics. Anopheles gambiae OBP1 and OBP4 were found capable of forming heterodimers possibly involved in the specific perception of the attractant indole. In order to understand how these OBPs interact in the presence of indole and to investigate the likelihood of a pH-dependent heterodimerization mechanism, the crystal structures of OBP4 at pH 4.6 and 8.5 were determined. Structural comparison to each other and with the OBP4-indole complex (3Q8I, pH 6.85) revealed a flexible N-terminus and conformational changes in the α4-loop-α5 region at acidic pH. Fluorescence competition assays showed a weak binding of indole to OBP4 that become further impaired at acidic pH. Additional Molecular Dynamic and Differential Scanning Calorimetry studies displayed that the influence of pH on OBP4 stability is significant compared to the modest effect of indole. Furthermore, OBP1-OBP4 heterodimeric models were generated at pH 4.5, 6.5, and 8.5, and compared concerning their interface energy and cross-correlated motions in the absence and presence of indole. The results indicate that the increase in pH may induce the stabilization of OBP4 by increasing its helicity, thereby enabling indole binding at neutral pH that further stabilizes the protein and possibly promotes the creation of a binding site for OBP1. A decrease in interface stability and loss of correlated motions upon transition to acidic pH may provoke the heterodimeric dissociation allowing indole release. Finally, we propose a potential OBP1-OBP4 heterodimer formation/disruption mechanism induced by pH change and indole binding.

}, issn = {1879-0003}, doi = {10.1016/j.ijbiomac.2023.125422}, author = {Mam, Bhavika and Tsitsanou, Katerina E and Liggri, Panagiota G V and Saitta, Francesca and Stamati, Evgenia C V and Mahita, Jarjapu and Leonis, George and Drakou, Christina E and Papadopoulos, Manthos and Arnaud, Philippe and Offmann, Bernard and Fessas, Dimitrios and Sowdhamini, Ramanathan and Zographos, Spyros E} } @article {78104, title = {A glance into the evolution of template-free protein structure prediction methodologies.}, journal = {Biochimie}, volume = {175}, year = {2020}, month = {2020 May 15}, pages = {85-92}, abstract = {

Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (\>150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform.

}, issn = {1638-6183}, doi = {10.1016/j.biochi.2020.04.026}, author = {Dhingra, Surbhi and Sowdhamini, Ramanathan and Cadet, Fr{\'e}d{\'e}ric and Offmann, Bernard} } @article {59713, title = {EcRBPome: a comprehensive database of all known E. coli RNA-binding proteins.}, journal = {BMC Genomics}, volume = {20}, year = {2019}, month = {2019 May 22}, pages = {403}, abstract = {

The repertoire of RNA-binding proteins (RBPs) in bacteria play a crucial role in their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome. It contains RBPs recorded from 614 complete E. coli proteomes available in the RefSeq database (as of October 2018). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download. To the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community.

}, issn = {1471-2164}, doi = {10.1186/s12864-019-5755-5}, author = {Ghosh, Pritha and Joshi, Adwait and Guita, Niang and Offmann, Bernard and Sowdhamini, R} }