Molecular dynamics, thermodynamic, and mutational binding studies for tumor-specific LyP-1 in complex with p32

TİMUR S. S., YALÇIN ÖZKAT G., Cevik O., Andac C., GÜRSOY R. N.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, vol.36, no.5, pp.1134-1144, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 5
  • Publication Date: 2018
  • Doi Number: 10.1080/07391102.2017.1313779
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1134-1144
  • Keywords: breast cancer, LyP-1, p32, molecular dynamics, MM-PBSA, ALA-SCAN, OXIDATIVE-PHOSPHORYLATION, MITOCHONDRIAL MATRIX, PROTEIN P32/GC1QR, HOMING PEPTIDE, CELL-SURFACE, LYMPHATICS, METABOLISM, SOFTWARE, DELIVERY, THERAPY
  • Ankara University Affiliated: No

Abstract

Recent studies in tumor homing peptides have shown the specificity of LyP-1 (CGNKRTRGC) to tumor lymphatics. In this present work, we evaluated the possible interactions between cyclic LyP-1 and its receptor, p32, with molecular dynamics and docking studies in order to lead the design of novel LyP-1 derivatives, which could bind to p32 more effectively and perform enhanced antitumor effect. The total binding enthalpy energies have been obtained by MM-PBSA thermodynamic computations and the favorability of p32.LyP-1 complex in water has been shown by explicit water MD computations. The last 30ns of molecular dynamics trajectory have shown the strong interaction of LyP-1 with the inner surface chains of p32, especially with chains B and C. ALA-SCAN mutagenesis studies have indicated the considerable influence of Asn3, Lys4, Arg5, and Arg7 amino acid residues on the specific binding of LyP-1. Within the knowledge of the critical role of p32 receptor in cancer cell metabolism, this study can lead to further developments in anticancer therapy by targeting p32 with LyP-1 derivatives as active targeting moiety. This data can also be applied for the development of new drug delivery systems in which LyP-1 can be used for its targeting and anticancer properties.