We are interested in understanding the relationship between movement and function in a protein, enzyme, virus, or aggregates of them. It is reasonable, as a number of theory groups contend, to develop methods that allow for the calculation of protein mobility and to compute the effect of key interactions such as hydrogen boding in a realistic manner. Our goal here is to bridge our ample expertise on molecular simulations with the biomedical and biomaterials areas to help increase the global knowledge to ultimately find cures for life-threatening diseases. In our recent work, we illustrated the possibilities of our theoretical and computational modeling research, and how it has already facilitated the understanding of some in vivo and in vitro experiments.
The tendency for globular proteins to aggregate causes their viscosity to increase with concentration much more rapidly than expected by simple models such as the Krieger-Dougherty equation. We use molecular simulations (both atomistic and mesoscale) as a complementary approach to investigate the role of protein size, net charge and dynamics on protein aggregation. We employ current theoretical methodology in a consistent manner using atomistic Molecular Dynamics (MD) and mesoscale technique Dissipative Particle Dynamics (DPD). Atomistic simulations allow us to understand the effect of the proteins’ dynamics on, for example, wild type and single mutations. Disulfide bonds can affect the stability of a protein, and thus its macroscopic properties in solution, especially the capability to form dimers and higher aggregates. With DPD we are able to assess the directions of collective motions, as they can be directly relevant to biological function and aggregation.
Finally, protein adsorption behavior has been a topic of intense research and great debate in the field of biomaterials surface science for decades. Experimentalists have studied the adsorption behavior of hundreds of different proteins on varying surfaces including metals, ceramics, glasses, synthetic polymers, natural polymers, and atop other proteins. Despite this extensive library of research, a fundamental understanding of protein adsorption remains uncertain. We utilize DPD to explore the adsorption behavior of model proteins in solution in the presence of surfaces of varying hydrophilicity, as shown on the right. Moreover, a quantitative explanation of adsorption and desorption kinetics is included.
- Effects of Galactosylation in Immunoglobulin G from All-Atom Molecular Dynamics Simulations
- Molecular Dynamics Simulations of Human Serum Albumin and Role of Disulfide Bonds
- Exploring the Dynamics of Four RNA-Dependent RNA Polymerases by a Coarse-Grained Model
- Chiral Elasticity of DNA
- Molecular Dynamics Simulations of the Viral RNA Polymerases Link Conserved and Correlated Motions of Functional Elements to Fidelity (cover article)
- Adsorption Behavior of Model Proteins on Surfaces
- Tissue Factor Around Dermal Vessels has Bound Factor VII in the Absence of Injury (feature article)