New binding mode of SLURP protein to α7 nicotinic acetylcholine receptor revealed by computer simulations
Diankin I. D., Kudryavtsev D. S., Zalevskij A. O., Tsetlin V. I., Golovin A. V.
Supercomputing Frontiers and Innovations
Vol.5, Issue4, P. 73-77
Опубликовано: 2018
Тип ресурса: Статья
Аннотация:
SLURP-1 is a member of three-finger toxin-like proteins. Their characteristic feature is a set of three beta strands extruding from hydrophobic core stabilized by disulfide bonds. Each betastrand carries a flexible loop, which is responsible for recognition. SLURP-1 was recently shown to act as an endogenous growth regulator of keratinocytes and tumor suppressor by reducing cell migration and invasion by antagonizing the pro-malignant effects of nicotine. This effect is achieved through allosteric interaction with α7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in an antagonist-like manner. Moreover, this interaction is unaffected by several well-known agents specifically alpha-bungarotoxin. In this work, we carry out the conformational analysis of the SLURP-1 by a microsecond-long full-atom explicit solvent molecular dynamics simulations followed by clustering, to identify representative states. To achieve this timescale we employed a GPU-accelerated version of GROMACS modeling
Ключевые слова:
Affinity propagation; Biomolecules; Clustering; Gromacs; Molecular dynamics; Protein docking
Binding energy; Biomolecules; Covalent bonds; Growth kinetics; Molecular dynamics; Proteins; Sulfur compounds; Tobacco; Affinity propagation; Clustering; Conformational analysis; Explicit solvent molecular dynamics; Gromacs; Nicotinic acetylcholine receptors; Protein docking; Structural variability; Clustering algorithms
Язык текста: Английский
ISSN: 2313-8734
Diankin I. D.
Kudryavtsev D. S.
Zalevskij A. O. Artur Olegovich 1990-
Tsetlin V. I.
Golovin A. V. Andrej Viktorovich 1975-
Дианкин И. Д.
Кудрявцев Д. С.
Залевский А. О. Артур Олегович 1990-
Цетлин В. И.
Головин А. В. Андрей Викторович 1975-
New binding mode of SLURP protein to α7 nicotinic acetylcholine receptor revealed by computer simulations
Текст визуальный непосредственный
Supercomputing Frontiers and Innovations
Южно-Уральский государственный университет (национальный исследовательский университет)
Vol.5, Issue4 P. 73-77
2018
Статья
Affinity propagation Biomolecules Clustering Gromacs Molecular dynamics Protein docking
Binding energy Biomolecules Covalent bonds Growth kinetics Molecular dynamics Proteins Sulfur compounds Tobacco Affinity propagation Clustering Conformational analysis Explicit solvent molecular dynamics Gromacs Nicotinic acetylcholine receptors Protein docking Structural variability Clustering algorithms
SLURP-1 is a member of three-finger toxin-like proteins. Their characteristic feature is a set of three beta strands extruding from hydrophobic core stabilized by disulfide bonds. Each betastrand carries a flexible loop, which is responsible for recognition. SLURP-1 was recently shown to act as an endogenous growth regulator of keratinocytes and tumor suppressor by reducing cell migration and invasion by antagonizing the pro-malignant effects of nicotine. This effect is achieved through allosteric interaction with α7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in an antagonist-like manner. Moreover, this interaction is unaffected by several well-known agents specifically alpha-bungarotoxin. In this work, we carry out the conformational analysis of the SLURP-1 by a microsecond-long full-atom explicit solvent molecular dynamics simulations followed by clustering, to identify representative states. To achieve this timescale we employed a GPU-accelerated version of GROMACS modeling