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Model‐free methods of analyzing domain motions in proteins from simulation: A comparison of normal mode analysis and molecular dynamics simulation of lysozyme
Author(s) -
Hayward Steven,
Kitao Akio,
Berendsen Herman J.C.
Publication year - 1997
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/(sici)1097-0134(199703)27:3<425::aid-prot10>3.0.co;2-n
Subject(s) - molecular dynamics , normal mode , lysozyme , domain (mathematical analysis) , statistical physics , dynamics (music) , mode (computer interface) , biological system , computer science , computational biology , chemistry , physics , computational chemistry , biology , mathematics , mathematical analysis , biochemistry , acoustics , vibration , operating system
Model‐free methods are introduced to determine quantities pertaining to protein domain motions from normal mode analyses and molecular dynamics simulations. For the normal mode analysis, the methods are based on the assumption that in low frequency modes, domain motions can be well approximated by modes of motion external to the domains. To analyze the molecular dynamics trajectory, a principal component analysis tailored specifically to analyze interdomain motions is applied. A method based on the curl of the atomic displacements is described, which yields a sharp discrimination of domains, and which defines a unique interdomain screw‐axis. Hinge axes are defined and classified as twist or closure axes depending on their direction. The methods have been tested on lysozyme. A remarkable correspondence was found between the first normal mode axis and the first principal mode axis, with both axes passing within 3 Å of the alpha‐carbon atoms of residues 2, 39, and 56 of human lysozyme, and near the interdomain helix. The axes of the first modes are overwhelmingly closure axes. A lesser degree of correspondence is found for the second modes, but in both cases they are more twist axes than closure axes. Both analyses reveal that the interdomain connections allow only these two degrees of freedom, one more than provided by a pure mechanical hinge. Proteins 27:425–437, 1997. © 1997 Wiley‐Liss, Inc.