A statistical approach to the interpretation of molecular dynamics simulations of calmodulin equilibrium dynamics
- Author(s)
- Likic, VA; Gooley, PR; Speed, TP; Strehler, EE;
- Details
- Publication Year 2005-12,Volume 14,Issue #12,Page 2955-2963
- Journal Title
- PROTEIN SCIENCE
- Publication Type
- Journal Article
- Abstract
- A sample of 35 independent molecular dynamics (MD) simulations of calmodulin (CaM) equilibrium dynamics was prepared from different but equally plausible initial conditions (20 simulations of the wild-type protein and 15 simulations of the D129N mutant). CaM's radius of gyration and backbone mean-square fluctuations were analyzed for the effect of the D129N mutation, and simulations were compared with experiments. Statistical tests were employed for quantitative comparisons at the desired error level. The computational model predicted statistically significant compaction of CaM relative to the crystal structure, consistent with the results of small-angle X-ray scattering (SAXS) experiments. This effect was not observed in several previously reported studies of (Ca2+)(4)-CaM, which relied on a single MD run. In contrast to radius of gyration, backbone mean-square fluctuations showed a distinctly non-normal and positively skewed distribution for nearly all residues. Furthermore, the D129N mutation affected the backbone dynamics in a complex manner and reduced the mobility of Glu123, Met124, Ile125, Arg126, and Glu127 located in the adjacent a-helix G. The implications of these observations for the comparisons of MD simulations with experiments are discussed. The proposed approach may be useful in studies of protein equilibrium dynamics where MD simulations fall short of properly sampling the conformational space, and when the comparison with experiments is affected by the reproducibility of the computational model.
- Publisher
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
- Keywords
- X-RAY-SCATTERING; BACKBONE DYNAMICS; DOMAIN MUTANT; CENTRAL HELIX; TROPONIN-C; PROTEINS; CALCIUM; BINDING; CONFORMATIONS; RESOLUTION
- Publisher's Version
- https://doi.org/10.1110/ps.051681605
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2005-12-01 12:00:00