Molecular dynamics simulations of ribonuclease T1. Effect of solvent on the interaction with 2'GMP.
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.
MacKerell
A D
AD
Department of Medical Biophysics, Karolinska Institutet, Stockholm, Sweden.
Rigler
R
R
Nilsson
L
L
Heinemann
U
U
Saenger
W
W
D004722:Endoribonucleases; D006150:Guanine Nucleotides; D006157:Guanosine Monophosphate; D008958:Models, Molecular; D006163:Ribonuclease T1; D012997:Solvents; D014867:Water
D006150:Guanine Nucleotides; D012997:Solvents; D014867:Water; D006157:Guanosine Monophosphate; D004722:Endoribonucleases; D006163:Ribonuclease T1