title: Molecular dynamics simulations of ribonuclease T1. Effect of solvent on the interaction with 2'GMP.
abstract: Molecular dynamics simulations in vacuum and with a water sphere around the active site were performed on the 2'GMP-RNase T1 complex. The presence of water led to the maintenance of the 2'-GMP-RNase T1 interactions as compared to the X-ray structure, including the hydrogen bonds implicated in the enzyme-inhibitor recognition process. The sidechain of His92 in the molecular dynamics water simulation, however, hydrogen bonds directly to the phosphate of 2'GMP in contrast to the X-ray structure but in support of the role of that residue in the enzyme's catalytic mechanism. Fluctuations of active-site residues are not strongly influenced by water, possibly owing to the exclusion of water by the bound 2'GMP, which did show an increase in mobility. Analysis of the 2'GMP-RNase T1 interactions versus time reveal an equilibrium fluctuation in the presence of water, leading to a less favorable 2'GMP-RNase T1 interaction energy, suggesting a possible relationship between picosecond fluctuations and inhibitor dissociation occurring in the millisecond time domain.
authors.affiliation: Department of Medical Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A D
authors.initials: AD
authors.lastname: MacKerell
authors.forename: R
authors.initials: R
authors.lastname: Rigler
authors.forename: L
authors.initials: L
authors.lastname: Nilsson
authors.forename: U
authors.initials: U
authors.lastname: Heinemann
authors.forename: W
authors.initials: W
authors.lastname: Saenger
mesh_terms: D004722:Endoribonucleases; D006150:Guanine Nucleotides; D006157:Guanosine Monophosphate; D008958:Models, Molecular; D006163:Ribonuclease T1; D012997:Solvents; D014867:Water
chemical_list: D006150:Guanine Nucleotides; D012997:Solvents; D014867:Water; D006157:Guanosine Monophosphate; D004722:Endoribonucleases; D006163:Ribonuclease T1