title: Statistical database analysis of the role of loop dynamics for protein-protein complex formation and allostery.
abstract: BACKGROUND
  Protein loops show rich conformational dynamics properties on a wide range of timescales as they play an essential role for many cellular functions during protein-protein interactions and recognition processes. However, little is known about the detail behavior of loops upon protein binding including allostery.
  
  
  RESULTS
  We report the loop motions and their dominant timescales for a library of 230 proteins that form protein-protein complexes using the ToeLoop predictor of loop dynamics. We applied the analysis to proteins in both their complex and free state and relate specific loop properties to their role in protein recognition. We observe a strong tendency of loops that move on relatively slow timescales of tens of ns to sub-μs to be directly involved in binding and recognition processes. Complex formation leads to a significant reduction in loop flexibility at the binding interface, but in a number of cases it can also trigger increased flexibility in distal loops in response to allosteric conformational changes. The importance of loop dynamics and allostery is highlighted by a case study of an antibody-antigen complex. Furthermore, we explored the relationship between loop dynamics and experimental binding affinities and found that a prevalence of high loop rigidity at the binding interface is an indicator of increased binding strength.
  
  
  METHODS
  http://spin.ccic.ohio-state.edu/index.php/toeloopppi.
  
  
  BACKGROUND
  bruschweiler.1@osu.edu.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
authors.forename: Yina
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Campus Chemical Instrument Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.|Campus Chemical Instrument Center, The Ohio State University, Columbus, OH, USA.|Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Brüschweiler
mesh_terms: D000495:Allosteric Site; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D012984:Software