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Dynamics of the Hck‐SH3 domain: Comparison of experiment with multiple molecular dynamics simulations
Author(s) -
Horita David A.,
Byrd R. Andrew,
Zhang Weixing,
Smithgall Thomas E.,
Gmeiner William H.
Publication year - 2000
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.9.1.95
Subject(s) - molecular dynamics , relaxation (psychology) , chemistry , dynamics (music) , physics , chemical physics , statistical physics , crystallography , computational chemistry , molecular physics , psychology , social psychology , acoustics
Molecular dynamics calculations provide a method by which the dynamic properties of molecules can be explored over timescales and at a level of detail that cannot be obtained experimentally from NMR or X‐ray analyses. Recent work (Philippopoulos M, Mandel AM, Palmer AG III, Lim C, 1997, Proteins 28 :481–493) has indicated that the accuracy of these simulations is high, as measured by the correspondence of parameters extracted from these calculations to those determined through experimental means. Here, we investigate the dynamic behavior of the Src homology 3 (SH3) domain of hematopoietic cell kinase (Hck) via 15 N backbone relaxation NMR studies and a set of four independent 4 ns solvated molecular dynamics calculations. We also find that molecular dynamics simulations accurately reproduce fast motion dynamics as estimated from generalized order parameter ( S 2 ) analysis for regions of the protein that have experimentally well‐defined coordinates (i.e., stable secondary structural elements). However, for regions where the coordinates are not well defined, as indicated by high local root‐mean‐square deviations among NMR‐determined structural family members or high B ‐factors/low electron density in X‐ray crystallography determined structures, the parameters calculated from a short to moderate length (less than 5–10 ns) molecular dynamics trajectory are dependent on the particular coordinates chosen as a starting point for the simulation.