title: Understanding the influence of guest-host interactions on the conformation of short peptides in a hydrophobic cavity: a computational study.
abstract: We performed a computational investigation to understand the conformational preferences of four short peptides in a self-assembled cage based on the experimental work by Y. Hatakeyama et al. (Angew. Chem. Int. Ed.2009, 48, 8695). For this purpose, we combined molecular dynamics simulations, Monte Carlo simulations, and quantum mechanical calculations to obtain energies and structures for several low-lying conformers of four peptides and the corresponding peptide-cage inclusion complexes. Our calculations at both B3LYP and MP2 levels show that for each peptide, the corresponding conformation within the host (as revealed by the crystal structure) does not represent the lowest-energy conformation of this peptide in vacuum. By comparing some low-lying conformers in vacuum and in the cavity (for the same peptide), we found that the cage has a significant influence on the conformational propensities of peptides. First, one carbonyl oxygen of each peptide tends to bind to one Zn(II) atom of the cage, forming a Zn-O bond. The formation of this bond leads to significant charge transfer from the cage to the peptide. Second, this Zn-O bond causes the peptide to go through some local conformational changes. For larger peptides, such as penta- and hexapeptides, our calculations also show that some of their conformers must undergo significant structural changes, due to the confinement of the host. This computational study reveals the noticeable influence of the guest-host interaction on the conformational preferences of short peptides.
authors: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University, Hankou Road 22, 210093 Nanjing, PR China.
authors: Weijie
authors: W
authors: Hua
authors: Lina
authors: L
authors: Xu
authors: Yi
authors: Y
authors: Luo
authors: Shuhua
authors: S
authors: Li
mesh_terms: D005740:Gases / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry
chemical_list: D005740:Gases; D010455:Peptides; D015032:Zinc