Implicit solvent models and free energies of solvation in the context of protein folding
department or school: Science, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Cumberworth, Alexander Michael
issued: 2016-04-30T00:00:00
issued: 2015
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Given the wide and fundamental roles proteins play in cells, as well as their potential medical and industrial applications, a detailed understanding of the relationships between sequence, structure, dynamics, and function is of critical importance. Molecular models are required to solve this problem, as well as models of the associated conformational spaces. One of the most challenging aspects of modeling these vast ensembles is the computer power required to carry out the requisite simulations. Reduced solvent models, and particularly a class referred to as implicit solvent models, have been developed extensively; however, they make many assumptions and approximations that are likely to affect accuracy. Here, several implicit solvent models commonly used for protein modeling are evaluated by comparing the expected changes in free energies of solvation upon folding ΔGsolv derived from micro--ms simulations of fast folding proteins to those given by the implicit solvent models. In the majority of cases, there is a significant and substantial difference between the ΔGsolv values calculated from the two approaches, with the implicit solvent models excessively favouring the folded state over the unfolded state. This could only be remedied by selecting values for the model parameters -- the internal dielectric constant for the polar term and the surface tension coefficient for the apolar term -- that were system specific or physically unrealistic.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/52833
note: Implicit solvent models and free energies of solvation inthe context of protein foldingbyAlexander Michael CumberworthB.Sc., The University of British Columbia, 2012A THESIS SUBMITTED IN PARTIAL FULFILLMENTOF THE REQUIREMENTS FOR THE DEGREE OFMaster of ScienceinTHE FACULTY OF GRADUATE AND POSTDOCTORALSTUDIES(Genome Science and Technology)The University of British Columbia(Vancouver)April 2015c© Alexander Michael Cumberworth, 2015AbstractGiven the wide and fundamental roles proteins play in cells, as well as their po-tential medical and industrial applications, a detailed understanding of the rela-tionships between sequence, structure, dynamics, and function is of critical im-portance. Molecular models are required to solve this problem, as well as modelsof the associated conformational spaces. One of the most challenging aspects ofmodeling these vast ensembles is the computer power required to carry out therequisite simulations. Reduced solvent models, and particularly a class referred toas implicit solvent models, have been developed extensively; however, they makemany assumptions and approximations that are likely to affect accuracy. Here, sev-eral implicit solvent models commonly used for protein modeling are evaluated bycomparing the expected changes in free energies of solvation upon folding ∆∆Gsolvderived from micro–ms simulations of fast folding proteins to those given by theimplicit solvent models. In the majority of cases, there is a significant and sub-stantial difference between the ∆∆Gsolv values calculated from the two approaches,with the implicit solvent models excessively favouring the folded state over theunfolded state. This could only be remedied by selecting values for the model pa-rameters – the internal dielectric constant for the polar term and the surface tensioncoefficient for the apolar term – that were system specific or physically unrealistic.iiPrefaceI was the lead investigator of all work presented, and composed the manuscript withinput …
has type: Thesis/Dissertation
date issued: 2015-05
is shown at: 10.14288/1.0166153
language: eng
degree discipline: Genome Science and Technology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
rights URI: http://creativecommons.org/licenses/by-nc-nd/2.5/ca/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/52833