Simulation studies of polypeptoids using replica exchange with dynamical scaling and dihedral biasing

Area of Science:

• Biochemistry
• Computational Chemistry
• Polymer Science

Background:

• Polypeptoids, unlike polypeptides, possess amide bonds with higher propensity for cis and trans conformations.
• The energy barrier for amide bond rotation hinders conventional molecular simulations in exploring these conformational states.

Purpose of the Study:

• To develop and present an efficient replica-exchange simulation method for overcoming the amide bond sampling problem in polypeptoids.
• To enhance the sampling of cis and trans conformations for polypeptoid oligomers.

Main Methods:

• A novel replica-exchange method utilizing three replicas: one at the target temperature/Hamiltonian, a high-temperature replica with biased dihedral potential, and a connecting replica.
• Application of the method to simulate short peptoid oligomers.

Main Results:

• The replica-exchange method successfully overcomes the energy barrier for amide bond rotation, enabling efficient sampling of both cis and trans conformations.
• Simulations revealed that short peptoid oligomers can adopt a wide range of conformations, from all-cis to all-trans.
• The average cis/trans ratio is influenced by side chain properties and the chosen potential model.

Conclusions:

• The presented replica-exchange method is effective for enhanced conformational sampling of polypeptoid amide bonds.
• This approach facilitates a deeper understanding of the structural diversity and conformational preferences in polypeptoid systems.
• Future studies can leverage this method to explore more complex polypeptoid structures and their properties.