Molecular dynamics simulations of rhodopsin point mutants at the cytoplasmic side of helices 3 and 6.
The present work reports on a structural analysis carried out through different computer simulations of a set of rhodopsin mutants with differential functional features in regard to the wild type. Most of these mutants, whose experimental features had previously been reported [Ramon et al. J Biol Chem 282, 14272-14282 (2007)], were designed to perturb a network of electrostatic interactions located at the cytoplasmic sides of transmembrane helices 3 and 6. Geometric and energetic features derived from the detailed analysis of a series of molecular dynamics simulations of the different rhodopsin mutants, involving positions 134(3.49), 247(6.30), and 251(6.34), suggest that the protein structure is sensitive to these mutations through the local changes induced that extend further to the secondary structure of neighboring helices and, ultimately, to the packing of the helical bundle. Overall, the results obtained highlight the complexity of the analyzed network of electrostatic interactions where the effect of each mutation on protein structure can produce rather specific features.
Cordomí
Arnau
A
Laboratori d'Enginyeria Molecular, Departament d'Enginyeria Química, Universitat Politècnica de Catalunya, Barcelona, Spain.
Ramon
Eva
E
Garriga
Pere
P
Perez
Juan J
JJ
D003198:Computer Simulation; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D017354:Point Mutation; D017433:Protein Structure, Secondary; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D014867:Water / Q000737:chemistry
D008055:Lipids; D012997:Solvents; D014867:Water; D012243:Rhodopsin