Coarse-Grained Molecular Dynamics Modeling of Interactions between Biomolecules and Nanostructures

Abstract

In modern biotechnology and medicine realm, understanding interactions between biomolecules and nanostructures at molecular level is essential for designs of nanoscale diagnostic or therapeutic devices. Due to the limited time and length scales a full-atomistic molecular dynamics system can reach, the coarse-grained molecular dynamics technique is continuously sought to describe interactions between biomolecules and nanostructures. Here, the coarse-grained molecular dynamics is applied to different cases for revealing complex interactions between biomolecules and nanostructures. The first case in this dissertation is to quantify the biomarker detection process, solve the puzzle of biosensor detection at ultralow concentration and expedite the technique of early cancer diagnosis. Antibodies have been used as bioreceptors in bio-diagnostic devices for decades, whose performances are affected by various factors such as orientation, density, and local environment. While there are extensive works on designing and fabrication of various biosensors, little is known about the molecular level interactions between antibodies coated on sensor surfaces and biomarkers suspended in medium. Thus, a coarse-grained model for biomarkers binding on an antibody-functionalized biosensor surface is constructed to study effects of surface properties and external parameters on antibody orientation and biomarkers binding time. The surface interaction type is found to significantly influence the antibody orientation and biomarker binding time. A proper electric field range is discovered to not only well-orientate antibodies but also steer biomarkers toward the surface, consequently reducing the binding time of biomarkers by two orders of magnitude. Moreover, a suitable surface coating density of antibodies has been proposed to help antibody orientation as well as biomarker binding. These findings can be used for rational design of biosensors with higher efficiency and more sensitive detections.For the subsequent cases, the coarse-grained molecular dynamics model for the DNA-NP conjugate which is assembled by DNA and nanoparticles is established and used as building blocks for constructing one dimensional nanoworm and two dimensional nanosheet structures. Their mechanical properties are tested and potential applications are discussed with the developed model. The nanoworm structure, which can be applied in fields of drug targeting, image probing and thermal therapies, has been assembled by DNA-nanoparticle conjugates. Subsequently, its mechanical properties have been investigated due to their importance on the structural stability, transport and circulations of the nanoworm. Stiffness and strengths of the nanoworm under different deformation types are studied by coarse-grained molecular dynamics simulations. Effects of temperature, DNA coating density and particle size on mechanical properties of nanoworms are also thoroughly investigated. Results show that both resistance and strength of the nanoworm are the weakest along the axial direction, indicating it is more prone to be ruptured by a stretching force. In addition, DNA strands are found to be more important than nanoparticles in determining mechanical properties of the nanoworm. Moreover, both strength and resistance in regardless of directions are proved to be enhanced by decreasing the temperature, raising the DNA coating density and enlarging the particle size. This study is capable of serving as guidance for designing nanoworms with optimal mechanical strengths for applications.Two dimensional arrays of DNA-nanoparticle conjugates have also been fabricated and become a promising platform for developments of chemical sensor, molecular circuit, and mechanical analysis tools. Whatever it is used for, the mechanical properties affect its efficiency and efficacy in large extent. Thus, its mechanical properties have been scrutinized by the coarse-grained molecular dynamics simulation model. Stress-strain curves of the lattice under shearing and stretching are obtained and analyzed. Different hairpin structures have been used to connect adjacent DNA-nanoparticle conjugates and proven to influence stress-strain relationship of 2D array. Effects of physical conditions such as the temperature and salt concentration on mechanical properties of the 2D lattice are also investigated. Results found that 2D lattice behave like a macroscopic paper or alumina foil, whose force-displacement curve is in great agreement with that of elastic sheet. The 2D nanosheet is quite stable at 293 K with a salt concentration of 100 mM. Based on aforementioned results, a numerical model is proposed for the stress-strain relationship of 2D array. In future, this numerical model will be evaluated by our experimental results.Future work includes the investigation on mechanical response of three dimensional nanocrystal constructed by the same DNA-NP conjugates and a multiscale modeling of red blood cell membrane rupturing process