Alanine-based peptides containing polar residues presumably favour α-helical structure entropically

Abstract

To evaluate the enthalpic and entropic contributions of polar residues in alanine-based peptides to α-helical propensities of peptides, we applied a Brownian dynamics simulation, together with the umbrella sampling, to two alanine-based 21-residue peptides: one composed of alanine only (AAA), the other composed of 18 alanines and 3 arginines (ARA). Higher α-helical propensity of ARA than that of AAA was obtained. However, they showed similar conformational stability in enthalpy, considering the contribution of the solvation energy and the potential energy. As an evaluation of entropic effects, the fluctuation of a dihedral angle, ψ, was investigated. Arginine residue showed smaller fluctuation than alanine in elongated states. Higher α-helical propensity might originate from entropic effects. Furthermore, arginine seems to affect the α-helical propensity of alanines interacting with arginine.

Keywords:

• alanine-based peptides
• α-helical propensity
• Brownian dynamics simulation
• umbrella sampling

Acknowledgements

We are grateful to MEXT for the financial support to W.K., I.Y. and T.A. for this work.