  In living organisms, proteins and peptides are often under the influence of
mechanical forces, especially in confined spaces such as membrane channels,
ribosome exit tunnel, or proteasome gate. Due to the directional nature of
proteins as polymers with distinct ends, forces have the potential to influence
protein conformational dynamics in a direction-dependent manner. In this study,
we employed force-probe molecular dynamics simulations to investigate the
impact of pulling a peptide through a confined environment versus pushing it in
the same direction. Our model involves a carbon nanotube and one of three
decapeptides with varying amino acid sequences. The simulations reveal that the
difference between pulling the C-terminus and pushing the N-terminus is
relatively minor when considering the conformational ensembles of the peptides.
The loading rate of the force probe and the amino acid sequence of the peptide
play a more important role. However, the application of force to the peptide
significantly influences the relative motion of the peptides with respect to
the nanotube. Pulling the peptide results in a smoother translocation through
the nanotube compared to pushing, although the internal conformational dynamics
of the peptide add complexity in either case. Our findings shed light on how
short peptides navigate confined spaces within the cellular environment,
emphasizing the importance of force-probe simulation studies in understanding
these processes.
