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.
Skip Nav Destination
CHORUS
Article navigation
28 October 2019
Research Article|
October 28 2019
Kinetics analysis of ubiquitin local fluctuations with Markov state modeling of the LE4PD normal modes
Special Collection:
Markov Models of Molecular Kinetics
Eric R. Beyerle
;
Eric R. Beyerle
Department of Chemistry and Biochemistry and Institute of Theoretical Science, University of Oregon
, Eugene, Oregon 97403, USA
Search for other works by this author on:
Marina G. Guenza
Marina G. Guenza
a)
Department of Chemistry and Biochemistry and Institute of Theoretical Science, University of Oregon
, Eugene, Oregon 97403, USA
Search for other works by this author on:
a)
Electronic mail: [email protected]
J. Chem. Phys. 151, 164119 (2019)
Article history
Received:
August 06 2019
Accepted:
October 06 2019
Citation
Eric R. Beyerle, Marina G. Guenza; Kinetics analysis of ubiquitin local fluctuations with Markov state modeling of the LE4PD normal modes. J. Chem. Phys. 28 October 2019; 151 (16): 164119. https://doi.org/10.1063/1.5123513
Download citation file:
Pay-Per-View Access
$40.00
Sign In
You could not be signed in. Please check your credentials and make sure you have an active account and try again.
Citing articles via
DeePMD-kit v2: A software package for deep potential models
Jinzhe Zeng, Duo Zhang, et al.
CREST—A program for the exploration of low-energy molecular chemical space
Philipp Pracht, Stefan Grimme, et al.
Freezing point depression of salt aqueous solutions using the Madrid-2019 model
Cintia P. Lamas, Carlos Vega, et al.
Related Content
Comparison between slow anisotropic LE4PD fluctuations and the principal component analysis modes of ubiquitin
J. Chem. Phys. (March 2021)
Identifying the leading dynamics of ubiquitin: A comparison between the tICA and the LE4PD slow fluctuations in amino acids’ position
J. Chem. Phys. (December 2021)
Predicting protein dynamics from structural ensembles
J. Chem. Phys. (November 2015)
Mode localization in the cooperative dynamics of protein recognition
J. Chem. Phys. (July 2016)
New force replica exchange method and protein folding pathways probed by force-clamp technique
J. Chem. Phys. (January 2008)