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Methods Mol Biol. 2018;1777:101-119. doi: 10.1007/978-1-4939-7811-3_5.

Replica Exchange Molecular Dynamics: A Practical Application Protocol with Solutions to Common Problems and a Peptide Aggregation and Self-Assembly Example.

Author information

1
Department of Physics, State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (MOE), Fudan University, Shanghai, P.R. China.
2
Department of Physics, State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (MOE), Fudan University, Shanghai, P.R. China. ghwei@fudan.edu.cn.
3
Basic Science Program, Leidos Biomedical Research, Inc. Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, USA.
4
Basic Science Program, Leidos Biomedical Research, Inc. Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, USA. nussinor@helix.nih.gov.
5
Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. nussinor@helix.nih.gov.

Abstract

Protein aggregation is associated with many human diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and type II diabetes (T2D). Understanding the molecular mechanism of protein aggregation is essential for therapy development. Molecular dynamics (MD) simulations have been shown as powerful tools to study protein aggregation. However, conventional MD simulations can hardly sample the whole conformational space of complex protein systems within acceptable simulation time as it can be easily trapped in local minimum-energy states. Many enhanced sampling methods have been developed. Among these, the replica exchange molecular dynamics (REMD) method has gained great popularity. By combining MD simulation with the Monte Carlo algorithm, the REMD method is capable of overcoming high energy-barriers easily and of sampling sufficiently the conformational space of proteins. In this chapter, we present a brief introduction to REMD method and a practical application protocol with a case study of the dimerization of the 11-25 fragment of human islet amyloid polypeptide (hIAPP(11-25)), using the GROMACS software. We also provide solutions to problems that are often encountered in practical use, and provide some useful scripts/commands from our research that can be easily adapted to other systems.

KEYWORDS:

Free energy landscape; GROMACS; Human islet amyloid polypeptide; Molecular dynamics simulations; Protein aggregation; REMD; Replica exchange method

PMID:
29744830
PMCID:
PMC6484850
DOI:
10.1007/978-1-4939-7811-3_5
[Indexed for MEDLINE]
Free PMC Article

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