Probing the Conformational Dynamics of the Bioactive Peptide TLQP-21 in Solution: A Molecular Dynamics Study.

VGF-derived peptide, TLQP-21, is a physiologically active neuropeptide exhibiting important roles in energy expenditure and balance, gastric contractility, reproduction, pain modulation, and stress. Although the physiological functions of the peptide constitute a research area of considerable interest, structural information is clearly lacking. Here, using extensive 550 nanoseconds molecular dynamics simulation in explicit water model, we have explored the folding energy landscape of the peptide. Principal component analysis and cluster analysis have been used to identify highly populated conformational states of the peptide in solution. The most populated structure of the peptide adopts a highly compact globular form stabilized by several hydrogen-bonding interactions and π-cationic interactions. Strong surface complementarity of hydrophobic residues allows tighter spatial fit of the residues within the core region of the peptide. Our simulation also predicts that the peptide is highly flexible in solution and that the region A7 -R9 and three C-terminal residues, P19 -R21 , possess strong helical propensity.