Domain Motions and the Open-to-Closed Conformational Transition of an Enzyme:  A Normal Mode Analysis ofS-Adenosyl-l-homocysteine Hydrolase†

Large-scale conformational changes are essential for proteins to function properly. Given that these transition events rarely occur, however, it is challenging to comprehend their underlying mechanisms through experimental and theoretical approaches. In this study, we propose a new computational methodology called internal coordinate normal mode-guided elastic network interpolation (ICONGENI) to predict conformational transition pathways in proteins. Its basic approach is to sample intermediate conformations by interpolating the interatomic distance between two end-point conformations with the degrees of freedom constrained by the low-frequency dynamics afforded by normal mode analysis in internal coordinates. For validation of ICONGENI, it is applied to proteins that undergo open-closed transitions, and the simulation results (i.e., simulated transition pathways) are compared with those of another technique, to demonstrate that ICONGENI can explore highly reliable pathways in terms of thermal and chemical stability. Furthermore, we generate an ensemble of transition pathways through ICONGENI and investigate the possibility of using this method to reveal the transition mechanisms even when there are unknown metastable states on rough energy landscapes.

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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

Proteins Structure Function and Bioinformatics ◽

10.1002/(sici)1097-0134(199703)27:3<425::aid-prot10>3.0.co;2-n ◽

1997 ◽

Vol 27 (3) ◽

pp. 425-437 ◽

Cited By ~ 192

Author(s):

Steven Hayward ◽

Akio Kitao ◽

Herman J.C. Berendsen

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Normal Mode ◽

Normal Mode Analysis ◽

Dynamics Simulation ◽

Mode Analysis ◽

Model Free ◽

Domain Motions

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Allosteric Conformational Transition in Adenylate Kinase: Dynamic Correlations and Implication for Allostery

Australian Journal of Chemistry ◽

10.1071/ch09449 ◽

2010 ◽

Vol 63 (3) ◽

pp. 405 ◽

Cited By ~ 8

Author(s):

Ming S. Liu ◽

Billy D. Todd ◽

Richard J. Sadus

Keyword(s):

Normal Mode ◽

Conformational Changes ◽

Adenylate Kinase ◽

Conformational Transition ◽

Normal Mode Analysis ◽

Coarse Grained ◽

Mode Analysis ◽

Elastic Network Model ◽

Protein Functions ◽

Correlated Motion

An essential aspect of protein science is to determine the deductive relationship between structure, dynamics, and various sets of functions. The role of dynamics is currently challenging our understanding of protein functions, both experimentally and theoretically. To verify the internal fluctuations and dynamics correlations in an enzyme protein undergoing conformational transitions, we have applied a coarse-grained dynamics algorithm using the elastic network model for adenylate kinase. Normal mode analysis reveals possible dynamical and allosteric pathways for the transition between the open and the closed states of adenylate kinase. As the ligands binding induces significant flexibility changes of the nucleotides monophosphate (NMP) domain and adenosine triphosphate (ATP) domain, the diagonalized correlation between different structural transition states shows that most correlated motions occur between the NMP domain and the helices surrounding the ATP domain. The simultaneous existence of positive and negative correlations indicates that the conformational changes of adenylate kinase take place in an allosteric manner. Analyses of the cumulated normal mode overlap coefficients and long-range correlated motion provide new insights of operating mechanisms and dynamics of adenylate kinase. They also suggest a quantitative dynamics criterion for determining the allosteric cooperativity, which may be applicable to other proteins.

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RAMAN SPECTRA OF TITANIUM DI-, TRI-, AND TETRA-CHLORIDES

International Journal of Modern Physics B ◽

10.1142/s021797920100886x ◽

2001 ◽

Vol 15 (28n30) ◽

pp. 3865-3868 ◽

Cited By ~ 2

Author(s):

H. MIYAOKA ◽

T. KUZE ◽

H. SANO ◽

H. MORI ◽

G. MIZUTANI ◽

...

Keyword(s):

Force Constant ◽

Raman Spectra ◽

Normal Mode ◽

Raman Band ◽

Normal Mode Analysis ◽

Force Constants ◽

Mode Analysis ◽

Oxidation Number

We have obtained the Raman spectra of TiCl n (n= 2, 3, and 4). Assignments of the observed Raman bands were made by a normal mode analysis. The force constants were determined from the observed Raman band frequencies. We have found that the Ti-Cl stretching force constant increases as the oxidation number of the Ti species increases.

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