Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Computational Investigation of the Free Energy Landscape of the four stereomers of Ac-L-Pro-c3Phe-NHMe (c3Phe=2,3-methanophenylalanine) in explicit and implicit Solvent

The prediction capabilities of atomistic simulations of peptides are hampered by different difficulties including, the reliability of force fields, the treatment of the solvent or the adequate sampling of the conformational space. The present report regards a computational study aimed at assessing the conformational profile of the four stereoisomers of the peptide Ace-Pro-c3Phe-NMe, previously reported to exhibit β-turn structures in dichloromethane with different type I/type II β-turn profiles (1).

For this purpose, we carried out a thorough sampling of the conformational space of the four peptides in explicit solvent using the replica exchange molecular dynamics method as a sampling technique and compared the results with simulations of the system modeled using the analytical linearized Poisson-Boltzmann (ALPB) method with two different AMBER force fields: parm96, and parm99SB.

The free energy landscapes of the different peptides computed in explicit solvent show two minima separated by high barriers and agree well with the published experimental results. The calculations carried out in implicit solvent do not describe the system in the same manner. Moreover, it is shown that implicit solvent calculations carried out with the parm96 force field agree better with those obtained with the parm99SB force field in explicit solvent (2,3). The results of the simulations suggest that the balance between intra- and intermolecular interactions is the cause of the differences between implicit and explicit solvent simulations in this system, stressing the role of the environment to define properly the conformational profile of a peptide in solution.


  1. A. I. Jimenez, C. Cativiela, A. Aubry, and M. Marraud, J Am Chem Soc 120, 9452–9459 (1998)
  2. A. Rodriguez, J. Canto, F. Corcho, and J.J. Perez, Biopolymers 92, 518-524, (2009)
  3. A. Rodriguez, P. Mokoema, F. Corcho, K. Bisetty and J. J. Perez, J. Phys. Chem. B, 115, 1440–1449 (2011)

Juan J. Perez
Alex Rodriguez
and Francesc Corcho

Department of Chemical Engineering Technical University of Catalonia Barcelona, Spain

Ph: +34 93 4016679
Fx: +34 93 4017150