title: Molecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides.
abstract: 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.
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Mao-jun
authors.initials: MJ
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Nan-xia
authors.initials: NX
authors.lastname: Xuan
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Zhi-cai
authors.initials: ZC
authors.lastname: Shang
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D006860:Hydrogen Bonding; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D033921:Vesicular Transport Proteins / Q000737:chemistry*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C120700:EHD1 protein, human; C486204:EPN2 protein, human; D010455:Peptides; D033921:Vesicular Transport Proteins
keywords: Binding affinity; EHD1 EH domain; Inhibitor design; Molecular dynamics simulation; Peptide