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Abstract The Membranome database provides comprehensive structural information on single‐pass (i.e., bitopic) membrane proteins from six evolutionarily distant organisms, including protein–protein interactions, complexes, mutations, experimental structures, and models of transmembrane α‐helical dimers. We present a new version of this database, Membranome 3.0, which was significantly updated by revising the set of 5,758 bitopic proteins and incorporating models generated by AlphaFold 2 in the database. The AlphaFold models were parsed into structural domains located at the different membrane sides, modified to exclude low‐confidence unstructured terminal regions and signal sequences, validated through comparison with available experimental structures, and positioned with respect to membrane boundaries. Membranome 3.0 was re‐developed to facilitate visualization and comparative analysis of multiple 3D structures of proteins that belong to a specified family, complex, biological pathway, or membrane type. New tools for advanced search and analysis of proteins, their interactions, complexes, and mutations were included. The database is freely accessible athttps://membranome.org.
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Structural compliance: A new metric for protein flexibility
Abstract Proteins are the active players in performing essential molecular activities throughout biology, and their dynamics has been broadly demonstrated to relate to their mechanisms. The intrinsic fluctuations have often been used to represent their dynamics and then compared to the experimental B‐factors. However, proteins do not move in a vacuum and their motions are modulated by solvent that can impose forces on the structure. In this paper, we introduce a new structural concept, which has been called the structural compliance, for the evaluation of the global and local deformability of the protein structure in response to intramolecular and solvent forces. Based on the application of pairwise pulling forces to a protein elastic network, this structural quantity has been computed and sometimes is even found to yield an improved correlation with the experimental B‐factors, meaning that it may serve as a better metric for protein flexibility. The inverse of structural compliance, namely the structural stiffness, has also been defined, which shows a clear anticorrelation with the experimental data. Although the present applications are made to proteins, this approach can also be applied to other biomolecular structures such as RNA. This present study considers only elastic network models, but the approach could be applied further to conventional atomic molecular dynamics. Compliance is found to have a slightly better agreement with the experimental B‐factors, perhaps reflecting its bias toward the effects of local perturbations, in contrast to mean square fluctuations. The code for calculating protein compliance and stiffness is freely accessible athttps://jerniganlab.github.io/Software/PACKMAN/Tutorials/compliance.
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- Award ID(s):
- 1661391
- PAR ID:
- 10456814
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Proteins: Structure, Function, and Bioinformatics
- Volume:
- 88
- Issue:
- 11
- ISSN:
- 0887-3585
- Page Range / eLocation ID:
- p. 1482-1492
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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