title: Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulations.
abstract: Formation of bacteriorhodopsin (bR) from apoprotein and retinal has been studied experimentally, but the actual pathway, including the point of entry, is little understood. Molecular dynamics simulations provide a surprisingly clear prediction. A window between bR helices E and F in the transmembrane part of the protein can be identified as an entry point for retinal. Steered molecular dynamics, performed by applying a series of external forces in the range of 200-1000 pN over a period of 0.2 ns to retinal, allows one to extract this chromophore from bR once the Schiff base bond to Lys216 is cleaved. Extraction proceeds until the retinal tail forms a hydrogen bond network with Ala144, Met145, and Ser183 side groups lining the exit/entry window. The manipulation induces a distortion with a fitted root mean square deviation of coordinates (ignoring retinal, water, and hydrogen atoms) of less than 1.9 A by the time the retinal carbonyl reaches the protein surface. The forces needed to extract retinal are due to friction and do not indicate significant potential barriers. The simulations therefore suggest a pathway for the binding of retinal. Water molecules are found to play a crucial role in the binding process.
authors.affiliation: Beckman Institute for Advanced Science and Technology, Center for Biophysics and Computational Biology, University of Illinois, Urbana 61801, USA.
authors.forename: B
authors.initials: B
authors.lastname: Isralewitz
authors.forename: S
authors.initials: S
authors.lastname: Izrailev
authors.forename: K
authors.initials: K
authors.lastname: Schulten
mesh_terms: D001436:Bacteriorhodopsins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D012172:Retinaldehyde / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D001436:Bacteriorhodopsins; C017827:bacterio-opsin; D012172:Retinaldehyde