View in EDS

Conformational Samplingof Peptides in the Presenceof Protein Crowders from AA/CG-Multiscale Simulations.

Saved in:
Bibliographic Details
Title: Conformational Samplingof Peptides in the Presenceof Protein Crowders from AA/CG-Multiscale Simulations.
Authors: Predeus, Alexander V.1, Gul, Seref1, Gopal, Srinivasa M.1, Feig, Michael1
Source: Journal of Physical Chemistry B. Jul2012, Vol. 116 Issue 29, p8610-8620. 11p.
Subjects: Conformational analysis, Peptides, Protein analysis, Multiscale modeling, Enthalpy, Molecular dynamics
Abstract: Macromolecular crowding is recognized as an importantfactor influencingfolding and conformational dynamics of proteins and nucleic acids.Previous views of crowding have focused on the mostly entropic volumeexclusion effect of crowding, but recent studies are indicating theimportance of enthalpic effects, in particular, changes in electrostaticinteractions due to crowding. Here, temperature replica exchange moleculardynamics simulations of trp-cage and melittin in the presence of explicitprotein crowders are presented to further examine the effect of proteincrowders on peptide dynamics. The simulations involve a three-componentmultiscale modeling scheme where the peptides are represented at anatomistic level, the crowder proteins at a coarse-grained level, andthe surrounding aqueous solvent as implicit solvent. This scheme optimallybalances a physically realistic description for the peptide with computationalefficiency. The multiscale simulations were compared with simulationsof the same peptides in different dielectric environments with dielectricconstants ranging from 5 to 80. It is found that the sampling in thepresence of the crowders resembles sampling with reduced dielectricconstants between 10 and 40. Furthermore, diverse conformational ensemblesare generated in the presence of crowders including partially unfoldedstates for trp-cage. These findings emphasize the importance of enthalpicinteractions over volume exclusion effects in describing the effectsof cellular crowding. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Physical Chemistry B is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
Description
Abstract:Macromolecular crowding is recognized as an importantfactor influencingfolding and conformational dynamics of proteins and nucleic acids.Previous views of crowding have focused on the mostly entropic volumeexclusion effect of crowding, but recent studies are indicating theimportance of enthalpic effects, in particular, changes in electrostaticinteractions due to crowding. Here, temperature replica exchange moleculardynamics simulations of trp-cage and melittin in the presence of explicitprotein crowders are presented to further examine the effect of proteincrowders on peptide dynamics. The simulations involve a three-componentmultiscale modeling scheme where the peptides are represented at anatomistic level, the crowder proteins at a coarse-grained level, andthe surrounding aqueous solvent as implicit solvent. This scheme optimallybalances a physically realistic description for the peptide with computationalefficiency. The multiscale simulations were compared with simulationsof the same peptides in different dielectric environments with dielectricconstants ranging from 5 to 80. It is found that the sampling in thepresence of the crowders resembles sampling with reduced dielectricconstants between 10 and 40. Furthermore, diverse conformational ensemblesare generated in the presence of crowders including partially unfoldedstates for trp-cage. These findings emphasize the importance of enthalpicinteractions over volume exclusion effects in describing the effectsof cellular crowding. [ABSTRACT FROM AUTHOR]
ISSN:15206106
DOI:10.1021/jp300129u