Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel

Abstract

A multiscale modeling approach is presented for the efficient construction of an equilibrated allatom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEGchain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications.

Molecular modeling to predict peptide accessibility for peptide-functionalized hydrogels

“…The details of the lattice, CG, and AA methods in each step of the toolset were introduced in a previous paper. 39 In a coarse-graining process, 44,45 several atoms are grouped together and represented by a bead with the mapping point being taken as the center of mass of each group of atoms. Figure 1 illustrates the strategy used to coarse-grain the two types of crosslinkers (PEGDA and MethG m RGDSP) and the copolymer network formed by them.…”

“…Bond-angle-bending and bond-rotation energy terms obtained in the CG force field were imposed in the system potential energy during the MC procedure of network generation to guide the local configuration of the lattice chain segments close to their equilibrium state of the off-lattice CG model. 39 The crosslinking process was modeled as a collision process in which crosslinking happens when two linkable chain ends meet (the distance between them is 2, ffiffi ffi 5 p , ffiffi ffi 6 p , or 3 lattice units). For each system, after the degree of crosslinking between all monomers reached the 97%, the on-lattice sampling process was stopped, and the final configuration was recorded and prepared for a transition to the off-lattice model.…”

“…To transfer the network structure from the lattice to the off-lattice models, the coordinates of the lattice points were scaled by a factor of 1.36 Å for length rescaling. 39 After transforming from the lattice model to the offlattice CG model, the final dimensions of the crosslinked surface structures were about 120 Â 120 Â 68 Å 3 . With this volume, we obtained 1.…”

“…To overcome the individual limitations of each method on its own, we recently developed and validated a modeling toolset designed specifically for the simulations of PF hydrogels. 39 The toolset consists of three consecutive parts: (1) building a global crosslinked PF hydrogel network using a "guided" lattice model based on Monte Carlo (MC) methods, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice CG model, and (3) recovering an AA structure of the PF hydrogel network by reverse mapping from the CG structure.…”

An Insight into Structural and Mechanical Properties of Ideal‐Networked Poly(Ethylene Glycol)–Peptide Hydrogels from Molecular Dynamics Simulations

“…The surface accessibility of peptides at the hydrogel–water interface was investigated as a function of tether length and peptide concentration. The approach in this study was based on earlier work from the same group where a multiscale approach combining lattice, CG, and atomistic methods was used to develop CG parameters for PEG‐based A‐B type copolymer hydrogels . Atomistic MD simulations have been used to determine the influence of several factors, including cross‐link density and water concentration, in hydrogel systems other than PEG on a wide range of properties .…”