Molecular Modeling and Simulations of Peptide–Polymer Conjugates

Abstract

Peptide–polymer conjugates are a class of soft materials composed of covalently linked blocks of protein/polypeptides and synthetic/natural polymers. These materials are practically useful in biological applications, such as drug delivery, DNA/gene delivery, and antimicrobial coatings, as well as nonbiological applications, such as electronics, separations, optics, and sensing. Given their broad applicability, there is motivation to understand the molecular and macroscale structure, dynamics, and thermodynamic behavior exhibited by such materials. We focus on the past and ongoing molecular simulation studies aimed at obtaining such fundamental understanding and predicting molecular design rules for the target function. We describe briefly the experimental work in this field that validates or motivates these computational studies. We also describe the various models (e.g., atomistic, coarse-grained, or hybrid) and simulation methods (e.g., stochastic versus deterministic, enhanced sampling) that have been used and the types of questions that have been answered using these computational approaches.

Supramolecular peptide nano-assemblies for cancer diagnosis and therapy: from molecular design to material synthesis and function-specific applications

“…In addition to the acceleration of the apoptosis for cancer cells, peptide-polymer conjugates have aroused great interest in the production of functional materials due to their selectivity and synergy [ 67 , 68 ]. For example, supramolecular polymers have recently attracted widespread attention, which are defined as the polymer arrays of monomer units held together by highly oriented and reversible non-covalent interactions, such as multiple hydrogen bonds, host–guest interactions, metal coordination interactions, and interaction with donor–acceptor.…”

“…In this way, the self-assembly of the cyclic peptide-polymer conjugate can be reversibly regulated. Considering that various functional polymers can be combined with cyclic peptides to construct various functions of tubular supramolecular polymers, the proposed strategy provided a new perspective on the preparation of finely controlled tubular structures and functionalized supramolecular polymers [ 68 ]. This peptide-based hybrid material has a sensitive response to various biological stimuli and was easy to integrate multiple biological functions such as cancer cell diagnosis and targeted drug delivery, exhibiting broad application prospects in biomedical community.…”

Application of Thermoresponsive Intrinsically Disordered Protein Polymers in Nanostructured and Microstructured Materials

“…While long ELPs are more common in the ELPs‐based materials, short ELPs are preferred in computational approaches because they are less complex and easier to model computationally. [ 108 ] Short ELPs attached to collagen‐like peptides (CLPs) have provided new molecules that enable the experimental observation of an LCST for short ELPs, and molecules that are also suitable for computational descriptions of the origins of the LCST behavior. Taylor et al.…”

Monomer‐scale design of functional protein polymers using consensus repeat sequences

“…Computational design approaches have already proven successful for de novo engineering of non-natural lattice-forming peptides [253][254][255] and predicting the assembly of peptide-polymer conjugates. [256][257][258] Finally, the boundaries of monomer-scale protein engineering are not necessarily defined by nature, but rather by the imaginations of polymer scientists and engineers. We foresee great potential in further integration of non-canonical amino acids 57,[259][260][261][262] and applying de novo protein design 263 to repeat proteins in the pursuit of biopolymeric materials with novel and tunable functions.…”