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Essential domain motions in barnase revealed by MD simulations
Author(s) -
Nolde Svetlana B.,
Arseniev Alexander S.,
Orekhov Vladislav Yu,
Billeter Martin
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10030
Subject(s) - barnase , hinge , domain (mathematical analysis) , biological system , energy landscape , molecular dynamics , mutant , mutation , protein domain , physics , chemistry , crystallography , biophysics , ribonuclease , biology , thermodynamics , computational chemistry , mathematics , classical mechanics , biochemistry , mathematical analysis , rna , gene
The wealth of data accumulated on the bacterial ribonuclease barnase is complemented by molecular dynamics trajectories starting from four different experimental structures and covering a total of >10 ns. Using principal component analysis, the simulations are interpreted in view of dynamic domains and hinges promoting relative motions of these domains. Two domains with residues 7–22 and 52–108 for the first domain and residues 25–51 for the second domain were consistently observed. Hinge regions consist primarily of Tyr24, Ser50, Ile51, and Gly52. Earlier mutation studies have demonstrated that the residues of the hinge regions play essential roles for the stability and activity of barnase. The domain motions are correlated to inter‐domain interactions involving functionally important active site residues, such as Lys27 and Glu73. A model is presented that combines the observation of dynamic domains and their motions with the extensive mutation data from the literature. Enthalpic energy contributions originating from specific inter‐domain interactions as well as entropic energy contributions due to the domain motions are discussed in the frame of this model and compared with destabilization energies measured for corresponding mutants. Proteins 2002;46:250–258. © 2002 Wiley‐Liss, Inc.