Molecular Dynamics Simulations of Protein Aggregation: Protocols for Simulation Setup and Analysis with Markov State Models and Transition Networks.

Autor:	Samantray S; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany., Schumann W; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany.; Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Illig AM; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany., Carballo-Pacheco M; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany., Paul A; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany., Barz B; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany.; Institute of Physical Biology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Strodel B; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany. b.strodel@fz-juelich.de.; Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. b.strodel@fz-juelich.de.
Jazyk:	angličtina
Zdroj:	Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2022; Vol. 2340, pp. 235-279.
DOI:	10.1007/978-1-0716-1546-1_12
Abstrakt:	Protein disorder and aggregation play significant roles in the pathogenesis of numerous neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. The end products of the aggregation process in these diseases are highly structured amyloid fibrils. Though in most cases, small, soluble oligomers formed during amyloid aggregation are the toxic species. A full understanding of the physicochemical forces that drive protein aggregation is thus required if one aims for the rational design of drugs targeting the formation of amyloid oligomers. Among a multitude of biophysical and biochemical techniques that are employed for studying protein aggregation, molecular dynamics (MD) simulations at the atomic level provide the highest temporal and spatial resolution of this process, capturing key steps during the formation of amyloid oligomers. Here we provide a step-by-step guide for setting up, running, and analyzing MD simulations of aggregating peptides using GROMACS. For the analysis, we provide the scripts that were developed in our lab, which allow to determine the oligomer size and inter-peptide contacts that drive the aggregation process. Moreover, we explain and provide the tools to derive Markov state models and transition networks from MD data of peptide aggregation. (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze:	MEDLINE
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