G-score : A function to solve the puzzle of modeling the protonation states of β-secretase binding pocket
(2018) In Journal of Molecular Graphics and Modelling 85. p.1-12- Abstract
The population density concept has emerged as a proposal for the analysis of molecular dynamics results, the key characteristic of population density is the evaluation of the simultaneous occurrence of a set of relevant parameters for a system. However, despite its statistical strength, selection of the tolerance level for the comparison of different models may appear as arbitrary. This work introduces the G-score, a function which summarizes and categorizes the results of population density analysis. Additionally, it incorporates parameters based on rmsd and dihedral angles, besides the protein-protein and protein-ligand interatomic distances conventionally used, which complement each other to provide a better description of the... (More)
The population density concept has emerged as a proposal for the analysis of molecular dynamics results, the key characteristic of population density is the evaluation of the simultaneous occurrence of a set of relevant parameters for a system. However, despite its statistical strength, selection of the tolerance level for the comparison of different models may appear as arbitrary. This work introduces the G-score, a function which summarizes and categorizes the results of population density analysis. Additionally, it incorporates parameters based on rmsd and dihedral angles, besides the protein-protein and protein-ligand interatomic distances conventionally used, which complement each other to provide a better description of the behavior of the system. These newly-proposed tools were applied to determine the most probable protonation state of the aspartic dyad of BACE1, Asp93 and Asp289, in the presence of three types of transition state inhibitors namely: reduced amides, tertiary carbinamines and hydroxyethylamines. The results show a full agreement between G-score values and population density charts, with the advantage of allowing a quick and direct comparison among all the considered models. We anticipate that the simplicity of calculating the parameters employed in this study will permit the extensive use of population density and the G-score for other molecular systems.
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- author
- Gueto-Tettay, Carlos LU ; Martinez-Consuegra, Alejandro ; Pelaez-Bedoya, Luis and Drosos-Ramirez, Juan Carlos
- organization
- publishing date
- 2018-10-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer, BACE1, G-score, GROMACS, Hydroxyethylamine, Molecular dynamics, Population density, Protonation state, Reduced amide, Tertiary carbinamine, TMoLiC
- in
- Journal of Molecular Graphics and Modelling
- volume
- 85
- pages
- 12 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:30053756
- scopus:85050182704
- ISSN
- 1093-3263
- DOI
- 10.1016/j.jmgm.2018.07.008
- language
- English
- LU publication?
- yes
- id
- b649dcdc-0c72-45dc-ae50-009af1f1a489
- date added to LUP
- 2018-08-15 08:09:35
- date last changed
- 2024-03-01 23:06:34
@article{b649dcdc-0c72-45dc-ae50-009af1f1a489,
abstract = {{<p>The population density concept has emerged as a proposal for the analysis of molecular dynamics results, the key characteristic of population density is the evaluation of the simultaneous occurrence of a set of relevant parameters for a system. However, despite its statistical strength, selection of the tolerance level for the comparison of different models may appear as arbitrary. This work introduces the G-score, a function which summarizes and categorizes the results of population density analysis. Additionally, it incorporates parameters based on rmsd and dihedral angles, besides the protein-protein and protein-ligand interatomic distances conventionally used, which complement each other to provide a better description of the behavior of the system. These newly-proposed tools were applied to determine the most probable protonation state of the aspartic dyad of BACE1, Asp93 and Asp289, in the presence of three types of transition state inhibitors namely: reduced amides, tertiary carbinamines and hydroxyethylamines. The results show a full agreement between G-score values and population density charts, with the advantage of allowing a quick and direct comparison among all the considered models. We anticipate that the simplicity of calculating the parameters employed in this study will permit the extensive use of population density and the G-score for other molecular systems.</p>}},
author = {{Gueto-Tettay, Carlos and Martinez-Consuegra, Alejandro and Pelaez-Bedoya, Luis and Drosos-Ramirez, Juan Carlos}},
issn = {{1093-3263}},
keywords = {{Alzheimer; BACE1; G-score; GROMACS; Hydroxyethylamine; Molecular dynamics; Population density; Protonation state; Reduced amide; Tertiary carbinamine; TMoLiC}},
language = {{eng}},
month = {{10}},
pages = {{1--12}},
publisher = {{Elsevier}},
series = {{Journal of Molecular Graphics and Modelling}},
title = {{G-score : A function to solve the puzzle of modeling the protonation states of β-secretase binding pocket}},
url = {{http://dx.doi.org/10.1016/j.jmgm.2018.07.008}},
doi = {{10.1016/j.jmgm.2018.07.008}},
volume = {{85}},
year = {{2018}},
}