Tripleurin XIIc: Peptide Folding Dynamics in Aqueous and Hydrophobic Environment Mimic Using Accelerated Molecular Dynamics

Molecules

Chetna Tyagi¹  András Szekeres¹  Tamás Marik¹  Csaba Vágvölgyi¹  László Kredics¹  Ferenc Ötvös² 

[1] Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Közép fasor 52, H-6726 Szeged, Hungary;Institute of Biochemistry, Biological Research Centre, Szeged, Temesvári krt. 62, H-6726 Szeged, Hungary;

关键词: peptaibols;    enhanced sampling;    molecular dynamics simulations;    solvent;    principal component analysis;    tripleurin;   

DOI  :  10.3390/molecules24020358

来源: DOAJ

【 摘 要 】

Peptaibols are a special class of fungal peptides with an acetylated N-terminus and a C-terminal 1,2-amino alcohol along with non-standard amino acid residues. New peptaibols named tripleurins were recently identified from a strain of the filamentous fungal species Trichoderma pleuroti, which is known to cause green mould disease on cultivated oyster mushrooms. To understand the mode of action of these peptaibols, the three-dimensional structure of tripleurin (TPN) XIIc, an 18-mer peptide, was elucidated using an enhanced sampling method, accelerated MD, in water and chloroform solvents. Non-standard residues were parameterized by the Restrained Electrostatic Potential (RESP) charge fitting method. The dihedral distribution indicated towards a right-handed helical formation for TPN XIIc in both solvents. Dihedral angle based principal component analysis revealed a propensity for a slightly bent, helical folded conformation in water solvent, while two distinct conformations were revealed in chloroform: One that folds into highly bent helical structure that resembles a beta-hairpin and another with an almost straight peptide backbone appearing as a rare energy barrier crossing event. The hinge-like movement of the terminals was also observed and is speculated to be functionally relevant. The convergence and efficient sampling is addressed using Cartesian PCA and Kullback-Leibler divergence methods.

【 授权许可】

Unknown