Martini Coarse-Grained Force Field:Extension to DNA

We systematically parameterized a coarsegrained (CG) model for DNA that is compatible with the Martini force field. The model maps each nucleotide into six to seven CG beads and is parameterized following the Martini philosophy. The CG nonbonded interactions are based on partitioning of the nudeobases between polar and nonpolar solvents as well as base base potential of mean force calculations. The bonded interactions are fit to single-stranded DNA (ssDNA) atomistic simulations and an elastic network is used to retain double-stranded DNA (dsDNA) and other specific DNA conformations. We present the implementation of the Martini DNA model and demonstrate the properties of individual bases, ssDNA as well as dsDNA, and DNA-protein complexes. The model opens up large-scale simulations of DNA interacting with a wide range of other (bio)molecules that are available within the Martini framework

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

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

Multiscale simulation of DNA

DNA is not only among the most important molecules in life, but a meeting point for biology, physics and chemistry, being studied by numerous techniques. Theoretical methods can help in gaining a detailed understanding of DNA structure and function, but their practical use is hampered by the multiscale nature of this molecule. In this regard, the study of DNA covers a broad range of different topics, from sub-Angstrom details of the electronic distributions of nucleobases, to the mechanical properties of millimeter-long chromatin fibers. Some of the biological processes involving DNA occur in femtoseconds, while others require years. In this review, we describe the most recent theoretical methods that have been considered to study DNA, from the electron to the chromosome, enriching our knowledge on this fascinating molecule

Molecular Dynamics Investigations of Structural Conversions in Transformer Proteins

Multifunctional proteins that undergo major structural changes to perform different functions are known as “Transformer Proteins”, which is a recently identified class of proteins. One such protein that shows a remarkable structural plasticity and has two distinct functions is the transcription antiterminator, RfaH. Depending on the interactions between its N-terminal domain and its C-terminal domain, the RfaH CTD exists as either an all-α-helix bundle or all-β-barrel structure. Another example of a transformer protein is the Ebola virus protein VP40 (eVP40), which exists in different conformations and oligomeric states (dimer, hexamer, and octamer), depending on the required function.I performed Molecular Dynamics (MD) computations to investigate the structural conversion of RfaH-CTD from its all-a to all-b form. I used various structural and statistical mechanics tools to identify important residues involved in controlling the conformational changes. In the full-length RfaH, the interdomain interactions were found to present the major barrier in the structural conversion of RfaH-CTD from all-a to all-b form. I mapped the energy landscape for the conformational changes by calculating the potential of mean force using the Adaptive Biasing Force and Jarzynski Equality methods. Similarly, the interdomain salt-bridges in the eVP40 protomer were found to play a critical role in domain association and plasma membrane (PM) assembly. This molecular dynamic simulation study is supported by virus like particle budding assays investigated by using live cell imaging that highlighted the important role of these saltbridges. I also investigated the plasma membrane association of the eVP40 dimer in various PM compositions and found that the eVP40 dimer readily associates with the PM containing POPS and PIP2 lipids. Also, the CTD helices were observed to be important in stabilizing the dimer-membrane complex. Coarse-grained MD simulations of the eVP40 hexamer and PM system revealed that the hexamer enhances the PIP2 lipid clustering at the lower leaflet of the PM. These results provide insight on the critical steps in the Ebola virus life cycle

A Review on Mechanics and Mechanical Properties of 2D Materials - Graphene and Beyond

Since the first successful synthesis of graphene just over a decade ago, a variety of two-dimensional (2D) materials (e.g., transition metal-dichalcogenides, hexagonal boron-nitride, etc.) have been discovered. Among the many unique and attractive properties of 2D materials, mechanical properties play important roles in manufacturing, integration and performance for their potential applications. Mechanics is indispensable in the study of mechanical properties, both experimentally and theoretically. The coupling between the mechanical and other physical properties (thermal, electronic, optical) is also of great interest in exploring novel applications, where mechanics has to be combined with condensed matter physics to establish a scalable theoretical framework. Moreover, mechanical interactions between 2D materials and various substrate materials are essential for integrated device applications of 2D materials, for which the mechanics of interfaces (adhesion and friction) has to be developed for the 2D materials. Here we review recent theoretical and experimental works related to mechanics and mechanical properties of 2D materials. While graphene is the most studied 2D material to date, we expect continual growth of interest in the mechanics of other 2D materials beyond graphene