FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Doruker, P
   Atilgan, AR
   Bahar, I
AF Doruker, P
   Atilgan, AR
   Bahar, I
TI Dynamics of proteins predicted by molecular dynamics simulations and
   analytical approaches: Application to alpha-amylase inhibitor
SO PROTEINS-STRUCTURE FUNCTION AND GENETICS
LA English
DT Article
DE correlated fluctuations; molecular dynamics simulations; beta-proteins;
   Gaussian network model; anisotropic effects; principal component
   analysis
ID NORMAL-MODE ANALYSIS; X-RAY-DIFFRACTION; COLLECTIVE MOTIONS;
   CONFIGURATIONAL ENTROPY; VIBRATIONAL DYNAMICS; COMPUTER-SIMULATION;
   SINGLE-PARAMETER; GLOBULAR PROTEIN; DOMAIN MOTIONS; LYSOZYME
AB The dynamics of alpha-amylase inhibitors has been investigated using molecular dynamics (IUD) simulations and two analytical approaches, the Gaussian network model (GNM) and anisotropic network model (ANM). MD simulations use a full atomic approach with empirical force fields, while the analytical approaches are based on a coarse-grained single-site-per-residue model with a single-parameter harmonic potential between sufficiently close (r less than or equal to 7 Angstrom) residue pairs. The major difference between the GNM and the ANM is that no directional preferences can be obtained in the GNM, all residue fluctuations being theoretically isotropic, while ANM does incorporate directional preferences. The dominant modes of motions are identified by (i) the singular value decomposition (SVD) of the MD trajectory matrices, and (ii) the similarity transformation of the Kirchhoff matrices of interresidue contacts in the GNM or ANM. The mean-square fluctuations of individual residues and the cross-correlations between domain movements retain the same characteristics, in all approaches-although the dispersion of modes and detailed amplitudes of motion obtained in the ANM conform more closely with MD results. The major weakness of the analytical approaches appears, on the other hand, to be their inadequacy to account for the anharmonic motions or multimeric transitions driven by the slowest collective mode observed in MD. Such motions usually suffer, however, from MD sampling inefficiencies, and multiple independent runs should be tested before making conclusions about their validity and detailed mechanisms. Overall this study invites attention to (i) the robustness of the average properties (mean-square fluctuations, cross-correlations) controlled by the low frequency motions, which are invariably reproduced in all approaches, and (ii) the utility and efficiency of the ANM, the computational time cost of which is of the order of "minutes" (real time), as opposed to "days" for MD simulations. Proteins 2000;40:512-524. (C) 2000 Wiley-Liss, Inc.
C1 Bogazici Univ, Sch Engn, Ctr Polymer Res, TR-80815 Bebek, Istanbul, Turkey.
   TUBITAK Adv Polymer Mat Res Ctr, Istanbul, Turkey.
RP Bahar, I (reprint author), Bogazici Univ, Sch Engn, Ctr Polymer Res, TR-80815 Bebek, Istanbul, Turkey.
RI Atilgan, Ali Rana/A-7805-2011
NR 55
TC 160
Z9 164
U1 2
U2 18
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD AUG 15
PY 2000
VL 40
IS 3
BP 512
EP 524
DI 10.1002/1097-0134(20000815)40:3<512::AID-PROT180>3.0.CO;2-M
PG 13
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 339XV
UT WOS:000088503900018
PM 10861943
ER

EF