Molecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides.

TitleMolecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides.
Publication TypeJournal Article
Year of Publication2015
AuthorsYu H, Wang M-jun, Xuan N-xia, Shang Z-cai, Wu J
JournalJ Zhejiang Univ Sci B
Date Published2015 Oct
KeywordsAdaptor Proteins, Vesicular Transport, Binding Sites, Hydrogen Bonding, Models, Chemical, Molecular Dynamics Simulation, Peptides, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Vesicular Transport Proteins

OBJECTIVE: To provide essential information for peptide inhibitor design, the interactions of Eps15 homology domain of Eps15 homology domain-containing protein 1 (EHD1 EH domain) with three peptides containing NPF (asparagine-proline-phenylalanine), DPF (aspartic acid-proline-phenylalanine), and GPF (glycine-proline-phenylalanine) motifs were deciphered at the atomic level. The binding affinities and the underlying structure basis were investigated.

METHODS: Molecular dynamics (MD) simulations were performed on EHD1 EH domain/peptide complexes for 60 ns using the GROMACS package. The binding free energies were calculated and decomposed by molecular mechanics/generalized Born surface area (MM/GBSA) method using the AMBER package. The alanine scanning was performed to evaluate the binding hot spot residues using FoldX software.

RESULTS: The different binding affinities for the three peptides were affected dominantly by van der Waals interactions. Intermolecular hydrogen bonds provide the structural basis of contributions of van der Waals interactions of the flanking residues to the binding.

CONCLUSIONS: van der Waals interactions should be the main consideration when we design peptide inhibitors of EHD1 EH domain with high affinities. The ability to form intermolecular hydrogen bonds with protein residues can be used as the factor for choosing the flanking residues.

Alternate JournalJ Zhejiang Univ Sci B
PubMed ID26465136
PubMed Central IDPMC4609540