Discontinuous Molecular Dynamics Simulations of Biomolecule Interfacial Behavior: Study of Ovispirin-1 Adsorption on a Graphene Surface

Abstract

Fundamental understanding of biomolecular interfacial behavior, such as protein adsorption at the microscopic scale, is critical to broad applications in biomaterials, nanomedicine, and nanoparticle-based biosensing techniques. The goal of achieving both computational efficiency and accuracy presents a major challenge for simulation studies at both atomistic and molecular scales. In this work, we developed a unique, accurate, high-throughput simulation method which, by integrating discontinuous molecular dynamics (DMD) simulations with the Golike protein−surface interaction model, not only solves the dynamics efficiently, but also describes precisely the protein intramolecular and intermolecular interactions at the atomistic scale and the protein−surface interactions at the coarse-grained scale. Using our simulation method and in-house developed software, we performed a systematic study of α-helical ovispirin-1 peptide adsorption on a graphene surface, and our study focused on the effect of surface hydrophobic interactions and π−π stacking on protein adsorption. Our DMD simulations were consistent with full-atom molecular dynamics simulations and showed that a single ovispirin-1 peptide lay down on the flat graphene surface with randomized secondary structure due to strong protein−surface interactions. Peptide aggregates were formed with an internal hydrophobic core driven by strong interactions of hydrophobic residues in the bulk environment. However, upon adsorption, the hydrophobic graphene surface can break the hydrophobic core by denaturing individual peptide structures, leading to disassembling the aggregate structure and further randomizing the ovispirin-1 peptide's secondary structures.

Molecular Structure of the Surface-Immobilized Super Uranyl Binding Protein

“…DMD simulations were performed using the software package (sDMD) developed by Zheng and co-workers. , In our simulations, the intra- and intermolecular interactions of protein(s) in the aqueous environment were represented precisely in an implicit water environment using well-calibrated all-atom DMD forcefield parameters published in the literature . Interactions between protein residues and the substrate surface were computed efficiently using the coarse-grained Go-like model − where N stands for the residues’ number in a protein, z i s is the distance between residue I and the surface, and σ i and ϵ i are the van der Waals parameters.…”

“…Compared with conventional MD simulations, − our DMD simulation combining the merits of both DMD simulations and Go-like model achieves better efficiency while offering acceptable accuracy. More details about the simulation algorithm of DMD simulations with the Go-like model for protein adsorption can be found in the recent publication from Zheng and Wei.…”

“…Since DMD is event-driven and the solvent is represented only implicitly, it is not straightforward to correlate the simulation time and the temperature with the real time and temperature . To address this issue, instead of applying the real units, we used time step t and reduced temperature T * = T / T s in the simulations . We assigned T s = 503.2 K because we set , where k B stands for Boltzmann’s constant, for Avogadro’s number, and E for one unit of energy, taken to be 1 kcal/mol .…”

“…86 To address this issue, instead of applying the real units, we used time step t and reduced temperature T* = T/T s in the simulations. 87 We assigned T s = 503.2 K because we set…”

“…, where k B stands for Boltzmann's constant, for Avogadro's number, and E for one unit of energy, taken to be 1 kcal/mol. 87 We chose T* = 0.5 (approximately 250 K) because at such a temperature the SUP protein does not denature in the bulk water. A protein was initially placed above the surface with a gapping distance of ∼2.0 nm with negligible protein−surface interactions.…”