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1. DOCKGROUND membrane protein-protein set

   https://doi.org/10.1371/journal.pone.0267531  

   Kotthoff, Ian; Kundrotas, Petras J.; Vakser, Ilya A. (May 2022, PLOS ONE)

   Soares, Claudio M. (Ed.)

   Membrane proteins are significantly underrepresented in Protein Data Bank despite their essential role in cellular mechanisms and the major progress in experimental protein structure determination. Thus, computational approaches are especially valuable in the case of membrane proteins and their assemblies. The main focus in developing structure prediction techniques has been on soluble proteins, in part due to much greater availability of the structural data. Currently, structure prediction of protein complexes (protein docking) is a well-developed field of study. However, the generic protein docking approaches are not optimal for the membrane proteins because of the differences in physicochemical environment and the spatial constraints imposed by the membranes. Thus, docking of the membrane proteins requires specialized computational methods. Development and benchmarking of the membrane protein docking approaches has to be based on high-quality sets of membrane protein complexes. In this study we present a new dataset of 456 non-redundant alpha helical binary interfaces. The set is significantly larger and more representative than the previously developed sets. In the future, it will become the basis for the development of docking and scoring benchmarks, similar to the ones for soluble proteins in the Dockground resource http://dockground.compbio.ku.edu . 

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2. Inhibiting the Keap1/Nrf2 Protein‐Protein Interaction with Protein‐Like Polymers

   https://doi.org/10.1002/adma.202311467  

   Carrow, Kendal P; Hamilton, Haylee L; Hopps, Madeline P; Li, Yang; Qiao, Baofu; Payne, N Connor; Thompson, Matthew P; Zhang, Xiaoyu; Magassa, Assa; Fattah, Mara; et al (May 2024, Advanced Materials)

   Successful and selective inhibition of the cytosolic protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein 1 (Keap1) can enhance the antioxidant response, with the potential for a therapeutic effect in a range of settings including in neurodegenerative disease (ND). Small molecule inhibitors have been developed, yet many have off-target effects, or are otherwise limited by poor cellular permeability. Peptide-based strategies have also been attempted to enhance specificity, yet face challenges due to susceptibility to degradation and lack of cellular penetration. Herein, these barriers are overcome utilizing a polymer-based proteomimetics. The protein-like polymer (PLP) consists of a synthetic, lipophilic polymer backbone displaying water soluble Keap1-binding peptides on each monomer unit forming a brush polymer architecture. The PLPs are capable of engaging Keap1 and displacing the cellular protective transcription factor Nrf2, which then translocates to the nucleus, activating the antioxidant response element (ARE). PLPs exhibit increased Keap1 binding affinity by several orders of magnitude compared to free peptides, maintain serum stability, are cell-penetrant, and selectively activate the ARE pathway in cells, including in primary cortical neuronal cultures. Keap1/Nrf2-inhibitory PLPs have the potential to impact the treatment of disease states associated with dysregulation of oxidative stress, such as NDs. 

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3. Structural motifs in protein cores and at protein–protein interfaces are different

   https://doi.org/10.1002/pro.3996  

   Hadarovich, Anna; Chakravarty, Devlina; Tuzikov, Alexander V.; Ben‐Tal, Nir; Kundrotas, Petras J.; Vakser, Ilya A. (February 2021, Protein Science)

   null (Ed.)
4. Modeling Electrostatic Force in Protein-Protein Recognition

   https://doi.org/10.3389/fmolb.2019.00094  

   Shashikala, H. B.; Chakravorty, Arghya; Alexov, Emil (September 2019, Frontiers in Molecular Biosciences)

   null (Ed.)
5. The intracellular environment affects protein–protein interactions

   https://doi.org/10.1073/pnas.2019918118  

   Speer, Shannon L.; Zheng, Wenwen; Jiang, Xin; Chu, I-Te; Guseman, Alex J.; Liu, Maili; Pielak, Gary J.; Li, Conggang (March 2021, Proceedings of the National Academy of Sciences)

   null (Ed.)

   Protein–protein interactions are essential for life but rarely thermodynamically quantified in living cells. In vitro efforts show that protein complex stability is modulated by high concentrations of cosolutes, including synthetic polymers, proteins, and cell lysates via a combination of hard-core repulsions and chemical interactions. We quantified the stability of a model protein complex, the A34F GB1 homodimer, in buffer, Escherichia coli cells and Xenopus laevis oocytes. The complex is more stable in cells than in buffer and more stable in oocytes than E. coli . Studies of several variants show that increasing the negative charge on the homodimer surface increases stability in cells. These data, taken together with the fact that oocytes are less crowded than E. coli cells, lead to the conclusion that chemical interactions are more important than hard-core repulsions under physiological conditions, a conclusion also gleaned from studies of protein stability in cells. Our studies have implications for understanding how promiscuous—and specific—interactions coherently evolve for a protein to properly function in the crowded cellular environment. 

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