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. 1997 Dec;73(6):2972–2979. doi: 10.1016/S0006-3495(97)78326-7

Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulations.

B Isralewitz 1, S Izrailev 1, K Schulten 1
PMCID: PMC1181203  PMID: 9414212

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.

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