G-score: A function to solve the puzzle of modeling the protonation states of β-secretase binding pocket
| Autor: | Carlos Gueto-Tettay, Luis Pelaez-Bedoya, Alejandro Martinez-Consuegra, Juan Carlos Drosos-Ramirez |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular 0301 basic medicine Work (thermodynamics) Protein Conformation Molecular Dynamics Simulation Dihedral angle Ligands Set (abstract data type) 03 medical and health sciences Molecular dynamics Catalytic Domain Materials Chemistry Statistical physics Physical and Theoretical Chemistry Spectroscopy Selection (genetic algorithm) Complement (set theory) Mathematics Binding Sites Function (mathematics) State (functional analysis) Computer Graphics and Computer-Aided Design Molecular Docking Simulation 030104 developmental biology Amyloid Precursor Protein Secretases Protons Algorithms Protein Binding |
| Zdroj: | Journal of Molecular Graphics and Modelling. 85:1-12 |
| ISSN: | 1093-3263 |
| DOI: | 10.1016/j.jmgm.2018.07.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect