| Autor: |
Beyerle ER; Department of Chemistry and Biochemistry and Institute of Theoretical Science, University of Oregon, Eugene, Oregon 97403, USA., Guenza MG; Department of Chemistry and Biochemistry and Institute of Theoretical Science, University of Oregon, Eugene, Oregon 97403, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of chemical physics [J Chem Phys] 2019 Oct 28; Vol. 151 (16), pp. 164119. |
| DOI: |
10.1063/1.5123513 |
| Abstrakt: |
Local fluctuations are important for protein binding and molecular recognition because they provide conformational states that can be trapped through a selection mechanism of binding. Thus, an accurate characterization of local fluctuations may be important for modeling the kinetic mechanism that leads to the biological activity of a protein. In this paper, we study the fluctuation dynamics of the regulatory protein ubiquitin and propose a novel theoretical approach to model its fluctuations. A coarse-grained, diffusive, mode-dependent description of fluctuations is accomplished using the Langevin Equation for Protein Dynamics (LE4PD). This equation decomposes the dynamics of a protein, simulated by molecular dynamics, into dynamical pathways that explore mode-dependent free energy surfaces. We calculate the time scales of the slow, high-amplitude fluctuations by modeling the kinetics of barrier crossing in the two-dimensional free energy surfaces using Markov state modeling. We find that the LE4PD predicts slow fluctuations in three important binding regions in ubiquitin: the C-terminal tail, the Lys11 loop, and the 50 s loop. These results suggest that the LE4PD can provide useful information on the role of fluctuations in the process of molecular recognition regulating the biological activity of ubiquitin. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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