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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. 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. (November 2020, Protein Science)

   Abstract Structures of proteins and protein–protein complexes are determined by the same physical principles and thus share a number of similarities. At the same time, there could be differences because in order to function, proteins interact with other molecules, undergo conformations changes, and so forth, which might impose different restraints on the tertiary versus quaternary structures. This study focuses on structural properties of protein–protein interfaces in comparison with the protein core, based on the wealth of currently available structural data and new structure‐based approaches. The results showed that physicochemical characteristics, such as amino acid composition, residue–residue contact preferences, and hydrophilicity/hydrophobicity distributions, are similar in protein core and protein–protein interfaces. On the other hand, characteristics that reflect the evolutionary pressure, such as structural composition and packing, are largely different. The results provide important insight into fundamental properties of protein structure and function. At the same time, the results contribute to better understanding of the ways to dock proteins. Recent progress in predicting structures of individual proteins follows the advancement of deep learning techniques and new approaches to residue coevolution data. Protein core could potentially provide large amounts of data for application of the deep learning to docking. However, our results showed that the core motifs are significantly different from those at protein–protein interfaces, and thus may not be directly useful for docking. At the same time, such difference may help to overcome a major obstacle in application of the coevolutionary data to docking—discrimination of the intramolecular information not directly relevant to docking. 

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3. 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.)
4. 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)

   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 colicells andXenopus laevisoocytes. The complex is more stable in cells than in buffer and more stable in oocytes thanE. 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 thanE. colicells, 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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5. Effects of SARS‐CoV‐2 mutations on protein structures and intraviral protein–protein interactions

   https://doi.org/10.1002/jmv.26597  

   Wu, Siqi; Tian, Chang; Liu, Panpan; Guo, Dongjie; Zheng, Wei; Huang, Xiaoqiang; Zhang, Yang; Liu, Lijun (April 2021, Journal of Medical Virology)

   null (Ed.)