title: An efficient null model for conformational fluctuations in proteins.
abstract: Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins.
authors.affiliation: The Bioinformatics Section, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Tim
authors.initials: T
authors.lastname: Harder
authors.forename: Mikael
authors.initials: M
authors.lastname: Borg
authors.forename: Sandro
authors.initials: S
authors.lastname: Bottaro
authors.forename: Wouter
authors.initials: W
authors.lastname: Boomsma
authors.forename: Simon
authors.initials: S
authors.lastname: Olsson
authors.forename: Jesper
authors.initials: J
authors.lastname: Ferkinghoff-Borg
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamelryck
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D003553:Cystine / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008049:Lipase / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012984:Software; D013482:Superoxide Dismutase / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D005656:Fungal Proteins; C082870:MTCP1 protein, human; D011518:Proto-Oncogene Proteins; D025801:Ubiquitin; D003553:Cystine; D013482:Superoxide Dismutase; D008049:Lipase; C431349:lipase B, Candida antarctica; D012259:Ribonuclease, Pancreatic