Native-Based Dissipative Particle Dynamics Approach for α-Helical Folding

Abstract

We developed a dissipative particle dynamics (DPD) approach that captures polyalanine folding into a stable helical conformation. Within the proposed native-based approach, the DPD parameters are derived based on the contact map constructed from the molecular dynamics (MD) simulations. We show that the proposed approach reproduces the folding of polypeptides of various lengths, including bundle formation for sufficiently long polypeptides. The proposed approach also allows one to capture the folding of the helical segments of the lysozyme. With further development of computationally efficient native-based DPD approaches for folding, modeling of a range of biomaterials incorporating α-helical segments could be extended to time and length scales far beyond those accessible in molecular dynamics simulations.

A Generic Force Field for Simulating Native Protein Structures Using Dissipative Particle Dynamics

“…However, the RMSD observed in our simulation is nearly 30% lower than the RMSD of lysozyme reported earlier. 58 Interestingly, as indicated in Fig. S5 in ESI, the root mean square fluctuations (RMSF data) in DPD simulation largely follow the trends observed in RMSF data obtained from AA simulation of lysozyme, lying well within ∼0.5 nm for most of the regions within the protein.…”

“…When compared with existing DPD models for proteins, 52–56,58 our proposed DPD force field reliably stabilizes a variety of protein secondary structures, reproduces native contacts, and captures protein folding to the native state. Our model alleviates the limitations present in previous Morse potential based DPD models 52–54 that have been used to predict secondary structures of proteins, and obviates the need to reparametrize potentials for specific protein structures.…”

“…When compared with existing DPD models for proteins, [52][53][54][55][56]58 our proposed DPD force field reliably stabilizes a variety of protein secondary structures, reproduces native contacts, and captures protein folding to the native state.…”

“…The dihedral potential has recently been used to stabilize the α helical structure in polyalanine. 58…”

“…In a very recent DPD study on folding of polyalanine into its native structure, the α -helix was stabilized by optimizing the repulsive force constant for the alanine residues that form the helical structure using the native contacts derived from atomistic simulations. 58 The dihedral potential was used to stabilize the helical structure. Nevertheless, the parameter set is polyalanine specific, and therefore the parameters need to be re-optimized for different proteins with varying secondary structures.…”