title: The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery.
abstract: Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.
authors.affiliation: Computational Biology Laboratory, Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center , Strandboulevarden 49, 2100 Copenhagen, Denmark.|Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen , 2200 Copenhagen, Denmark.
authors.forename: Elena
authors.initials: E
authors.lastname: Papaleo
authors.affiliation: Department of Chemistry, University College London , London WC1E 6BT, United Kingdom.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Saladino
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca , Piazza della Scienza 2, 20126 Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambrughi
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen , 2200 Copenhagen, Denmark.
authors.forename: Kresten
authors.initials: K
authors.lastname: Lindorff-Larsen
authors.affiliation: Department of Chemistry, University College London , London WC1E 6BT, United Kingdom.
authors.forename: Francesco Luigi
authors.initials: FL
authors.lastname: Gervasio
authors.affiliation: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute Frederick , Frederick, Maryland 21702, United States.|Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine Sackler School of Medicine, Tel Aviv University , Tel Aviv 69978, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000494:Allosteric Regulation; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011506:Proteins; D011494:Protein Kinases; D007781:Lactoferrin