title: Computational Assessment of Potassium and Magnesium Ion Binding to a Buried Pocket in GTPase-Associating Center RNA.
abstract: An experimentally well-studied model of RNA tertiary structures is a 58mer rRNA fragment, known as GTPase-associating center (GAC) RNA, in which a highly negative pocket walled by phosphate oxygen atoms is stabilized by a chelated cation. Although such deep pockets with more than one direct phosphate to ion chelation site normally include magnesium, as shown in one GAC crystal structure, another GAC crystal structure and solution experiments suggest potassium at this site. Both crystal structures also depict two magnesium ions directly bound to the phosphate groups comprising this controversial pocket. Here, we used classical molecular dynamics simulations as well as umbrella sampling to investigate the possibility of binding of potassium versus magnesium inside the pocket and to better characterize the chelation of one of the binding magnesium ions outside the pocket. The results support the preference of the pocket to accommodate potassium rather than magnesium and suggest that one of the closely binding magnesium ions can only bind at high magnesium concentrations, such as might be present during crystallization. This work illustrates the complementary utility of molecular modeling approaches with atomic-level detail in resolving discrepancies between conflicting experimental results.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, The University of Utah , 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112-5820, United States.
authors.forename: Hamed S
authors.initials: HS
authors.lastname: Hayatshahi
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, The University of Utah , 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112-5820, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Roe
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, The University of Utah , 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112-5820, United States.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Hall
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, The University of Utah , 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112-5820, United States.
authors.forename: Thomas E
authors.identifier: 0000-0003-0298-3904
authors.initials: TE
authors.lastname: Cheatham
mesh_terms: D001665:Binding Sites; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007477:Ions; D012313:RNA; D020558:GTP Phosphohydrolases; D008274:Magnesium; D011188:Potassium