Hybrid Particle-Field Model for Conformational Dynamics of Peptide Chains

Abstract

We propose the first model of a polypeptide chain based on a hybrid-particle field approach. The intramolecular potential is built on a two-bead coarse grain mapping for each amino acid. We employ a combined potential for the bending and the torsional degrees of freedom that ensures the stabilization of secondary structure elements in the conformational space of the polypeptide. The electrostatic dipoles associated with the peptide bonds of the main chain are reconstructed by a topological procedure. The intermolecular interactions comprising both the solute and the explicit solvent are treated by a density functional-based mean-field potential. Molecular dynamics simulations on a series of test systems show how the model here introduced is able to capture all the main features of polypeptides. In particular, homopolymers of different lengths yield a complex folding phase diagram, covering from the collapsed to swollen state. Moreover, simulations on models of a four-helix bundle and of an alpha + beta peptide evidence how the collapse of the hydrophobic core drives the appearance of both folded motifs and the stabilization of tertiary or quaternary assemblies. Finally, the polypeptide model is able to structurally respond to the environmental changes caused by the presence of a lipid bilayer.

Hybrid Particle-Field Molecular Dynamics Simulations of Charged Amphiphiles in an Aqueous Environment

“…74,75 The ability of hPF models to treat explicit electrostatics in good agreement with experiment opens up the possibility of simulating efficiently biological moieties where the polyelectrolyte character is dominant; for example, combining it to proposed models for polypeptides with explicit electrostatics. [76][77][78][79] Finally, our analysis points to the importance of carefully calibrating ɛ r in studies that aim to determine dynamic or structural properties of soft matter assemblies, especially in very specific thermodynamic conditions.…”

The elixir phase of chain molecules

“…Nevertheless, the approximate structures can be exploited by using the ground states of the elixir phase may be used as computationally efficient starting points for more refined calculations 42,43 that introduce additional chemical details. It would be extremely interesting to combine the present strategy with complementary coarse-grained approaches that have been proposed recently in the literature [44][45][46][47] to shed new light on the nature of protein folding pathway. 38,39 A cell is not just a container of ordinary molecules-rather, it consists of incredibly powerful interacting molecular machines that orchestrate life.…”

Atomistic hybridparticle‐fieldmolecular dynamics combined withslip‐springs: Restoring entangled dynamics to simulations of polymer melts

“…[ 10,11 ] After the integration of electrostatics, [ 12,13 ] the hPF‐MD method was further successfully applied in charged systems particularly of polyelectrolytes, charged amphiphiles [ 14 ] and polypeptides. [ 15 ]…”

“…[10,11] After the integration of electrostatics, [12,13] the hPF-MD method was further successfully applied in charged systems particularly of polyelectrolytes, charged amphiphiles [14] and polypeptides. [15] The hPF-MD method has, therefore, been around for a decade, and its capabilities and shortcomings are well-known. We will discuss them in this contribution only, as far as needed for our redevelopment, and otherwise refer the reader to the existing literature.…”

“…We will discuss them in this contribution only, as far as needed for our redevelopment, and otherwise refer the reader to the existing literature. [2,5,7,8,15] The problem of incorrect chain crossability also arises in very CG polymer models, since from a certain degree of coarse-graining onward, interactions necessarily become soft-core. [1] To recover the chain entanglements in simulations with such soft nonbonded interactions, several attempts have been reported.…”