Simulating ligand-induced conformational changes in proteins using a mechanical disassembly method.
Simulating protein conformational changes induced or required by the internal diffusion of a ligand is important for the understanding of their interaction mechanisms. Such simulations are challenging for currently available computational methods. In this paper, the problem is formulated as a mechanical disassembly problem where the protein and the ligand are modeled like articulated mechanisms, and an efficient method for computing molecular disassembly paths is described. The method extends recent techniques developed in the framework of robot motion planning. Results illustrating the capacities of the approach are presented on two biologically interesting systems involving ligand-induced conformational changes: lactose permease (LacY), and the beta(2)-adrenergic receptor.
CNRS, LAAS, 7 avenue du colonel Roche, F-31077 Toulouse, France. juan.cortes@laas.fr
Juan
J
Cortés
Duc Thanh
DT
Le
Romain
R
Iehl
Thierry
T
Siméon
D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D004058:Diffusion; D006860:Hydrogen Bonding; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry*
D008024:Ligands; D026901:Membrane Transport Proteins; D018343:Receptors, Adrenergic, beta-2; C021499:lactose permease