Computational modeling of constitutively active mutants of GPCRs C5a receptor.
In the past decade, an increasing number of studies using computational modeling procedures have focused on the structural aspects of constitutive activity in G protein-coupled receptors (GPCRs). This chapter reviews various conceptual approaches in computational modeling of constitutively active mutants (CAMs) including analyzing three-dimensional models of the ground states of GPCRs based on structural homology with the known X-ray templates; molecular dynamics simulations starting from the ground states; and modeling of CAMs based on the experimentally suggested templates of the possible activated states. The developed buildup procedure of rotational sampling of the TM regions of GPCRs is highlighted in more detail. Experimental data on CAMs of the complement factor 5a receptor (C5aR) are used to validate the rotational sampling results.
MolLife Design LLC, St. Louis, Missouri, USA.
Gregory V
GV
Nikiforovich
Thomas J
TJ
Baranski
D056004:Molecular Dynamics Simulation / Q000639:trends; D009154:Mutation; D011487:Protein Conformation; D044087:Receptor, Anaphylatoxin C5a / Q000737:chemistry / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics*
D044087:Receptor, Anaphylatoxin C5a; D043562:Receptors, G-Protein-Coupled