  In this study, we investigate interactions of extended conformations of
homodimeric peptides made of small (glycine or alanine) and large hydrophobic
(valine or leucine) sidechains using all-atom molecular dynamics simulations to
decipher driving forces for \beta-sheet formation. We make use of a periodic
boundary condition setup in which individual peptides are infinitely long and
stretched. Dimers adopt \beta-sheet conformations at short interpeptide
distances (\xi ~ 0.5 nm) and at intermediate distances (~ 0.8 nm), valine and
leucine homodimers assume cross-\beta-like conformations with side chains
interpenetrating each other. These two states are identified as minima in the
Potential of Mean Force (PMF). While the number of interpeptide hydrogen bonds
increases with decreasing interpeptide distance, the total hydrogen bond number
in the system does not change significantly, suggesting that formation of
\beta-sheet structures from extended conformations is not driven by hydrogen
bonds. This is supported by an increase in electrostatic energy at short
interpeptide distances. A remarkable correlation between the volume of the
system and the total electrostatic energy is observed, further reinforcing the
idea that excluding water in proteins comes with an enthalpic penalty. We also
discuss microscopic mechanisms accounting for \beta-sheet formation based on
computed enthalpy and entropy and we show that they are different for peptides
with small and large side chains.
