1. Molecular dynamics, thermodynamic, and mutational binding studies for tumor-specific LyP-1 in complex with p32.
- Author
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Timur SS, Yalçın G, Çevik Ö, Andaç C, and Gürsoy RN
- Subjects
- Binding Sites, Carrier Proteins metabolism, Humans, Mitochondrial Proteins metabolism, Molecular Docking Simulation, Peptides, Cyclic metabolism, Protein Binding, Protein Conformation, Structure-Activity Relationship, Carrier Proteins chemistry, Carrier Proteins genetics, Mitochondrial Proteins chemistry, Mitochondrial Proteins genetics, Molecular Dynamics Simulation, Mutation, Peptides, Cyclic chemistry, Peptides, Cyclic genetics, Thermodynamics
- 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 30 ns 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.
- Published
- 2018
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