Dramatic differences in the motions of the mouth of open and closed cytochrome P450BM-3 by molecular dynamics simulations
Article first published online: 3 FEB 2004
Copyright © 1995 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 21, Issue 3, pages 237–243, March 1995
How to Cite
Paulsen, M. D. and Ornstein, R. L. (1995), Dramatic differences in the motions of the mouth of open and closed cytochrome P450BM-3 by molecular dynamics simulations. Proteins, 21: 237–243. doi: 10.1002/prot.340210306
- Issue published online: 3 FEB 2004
- Article first published online: 3 FEB 2004
- Manuscript Accepted: 14 NOV 1994
- Manuscript Received: 24 MAY 1994
- domain motions;
- crystal packing effects;
- protein dynamics;
- enzyme dynamics
Molecular dynamics trajectories were calculated separately for each of the two molecules in the asymmetric unit of the crystal structure of the hemoprotein domain of cytochrome P450BM-3. Each simulation was 200 ps in length and included a 10 Å layer of explicit solvent. The simulated time-average structure of each P450BM-3 molecule is closer to its crystal structure than the two molecular dynamics time-averaged structures are to each other. In the crystal structure, molecule 2 has a more accessible substrate binding pocket than molecule 1, and this difference is maintained throughout the simulations presented here. In particular, the substrate docking regions of molecule 1 and molecule 2 diverge in the solution state simulations. The mouth of the substrate binding pocket is significantly more mobile in the simulation of molecule 2 than in the simulation of molecule 1. For molecule 1, the width of the mouth is only slightly larger than its X-ray value of 8.7 Å and undergoes fluctuations of about 1 Å. However, in molecule 2, the mouth of the substrate binding pocket is dramatically more open in the time-average molecular dynamics structure (14.7 Å) than in the X-ray structure (10.9 Å). Furthermore, this region of the protein undergoes large amplitude motions during the trajectory that are not seen in the trajectory of molecule 1, repeatedly opening and closing up to 7 Å. Presumably, the binding of different substrates will induce the mouth region to adopt different conformations from within the wide range of structures that are accessible. © 1995 Wiley-Liss, Inc.