The current status of the ab initio calculations for the electronic states, stable structures and dynamics of DNA and associated molecular systems is reviewed. Using computational tools such as the fragment molecular orbital method, the (ab initio and classical) molecular dynamics method and the charge equilibration method, we are analyzing the mechanism of transcriptional regulation in which the molecular recognition between DNA and proteins plays a vital role. In addition, we are studying the electron transfer or transport properties of DNA which have recently attracted considerable attention in the context of radiation biology and nanotechnology applications. In these problems, the interfaces among DNA, proteins, ligand molecules, solvent, counter ions and electrodes are often essential for their relevant functions. The theoretical issues remaining to be elucidated are also addressed.
DNA chips have been much interested in the detection and the analysis of genes because the sequence of human genome has been determined by the worldwide human genome project. GeneChip (Affimetrix Co.) is the most popular DNA chip, but is very expensive and needs a huge fluorescence detection equipment. We have been developing an electrochemical gene detection method, named as DNA sensor, in order to supply an easy and cheap device of the gene detection. In recent years, we have focused on the application of the DNA sensor to DNA chip aiming at the bed-side diagnosis of genes. We introduce here the outline of the DNA sensor and the electrochemical DNA chip for the assessment of interferon therapy in hepatitis C patients.
DNA is one of the most promising molecules as the building bolcks in molecular nanotechnology and nanoelectronics. The investigations of DNA on the nanostructure, electrical conductivity and electronic states have significant implications for the application of DNA in electronic devices and in DNA-based electrochemical biosensors. The intrinsic electrical properties and actual nanostructures of polynucleotides, such as self-assembled DNA network and DNA films have been investigated using a nano-gap electrode and photoemission spectroscopy, SPM techniques, etc. Poly[d(G-C)]2, poly(dG)·poly(dC) constructs the uniform two-dimensional network structure on mica and SiO2/Si surfaces. The conductivity of these molecules has been successfully controlled by chemical doping. The dG-dC pairs provide conduction properties upon I2 doping while dA-dT pairs do not. It is found that the poly(dG)·poly(dC) may have hole conductivity. The conduction mechanism based on the charge hopping model is discussed.
Recent topics of the chemical/biochemical micro/nanosystems using MEMS technologies and top down nanotechnologies are reviewed. This field is called Micro Total Analysis Systems (μTAS), the Lab-on-a-Chip and BioMEMS. The largest international academic conference of this field, Micro Total Analysis Systems (μTAS 2002), was held in Nara, Japan last November. A general trend in the conference is analyzed and described. Some noteworthy papers concerning the technologies of biomolecule handling and separation are picked up and introduced.
In the post-genome sequencing era, “Structural Genomics” has become one of the most important research fields in life science. Here I introduce the outline of the study of structural genomics in RIKEN Genomic Sciences Center and also the connection between surface science and structural genomics. Structural genomics is an emerging research field, which examines the enormous amounts of information stored in the genomes of living organisms. We are trying to determine a variety of three-dimensional structures of protein mainly by NMR and also to analyze the structure-function relationship of the proteins systematically and comprehensively. In the process of protein function analysis, molecular interaction analysis is very important and we use various methods including in silico screening, mass spectrometry, surface plasmon resonance, NMR, and so on. All of these analytical methods are based on protein-ligand interaction on molecular surfaces.
Various thermodynamic databases have been compiled to be mainly applied to the calculation of phase diagrams of alloys, ceramics and so on. The accumulation and assessment of thermodynamic data and phase equilibrium information to establish those databases is sometimes called CALPHAD (Computer Calculation of Phase Diagrams) approach. The CALPHAD has been recognized to be useful in various aspects of materials science and engineering. If the thermodynamic databases could be used to evaluate surface properties of liquid solutions as well as phase equilibria, we would be able to widen not only the applicability of those thermodynamic databases but also the further understanding of the surface properties of liquid alloys and molten ionic mixtures. On the basis of the above concepts, we have applied the thermodynamic databases to the calculation of the surface tension of liquid alloys and molten ionic mixtures. In this paper, we described some of the examples obtained from the above evaluation of the surface properties.
Adsorbed nano-meter scale species are markedly influenced by weak local interaction including strain. Stability of nano-scale construction on the surface is crucially influenced by such weak interaction but the direct observation by ordinary experimental method is difficult. Scanning electron microscopy (STM) provides not only high resolution in real space but also direct information about the interactions and the strain or stress. As discussed in this paper, the weak interaction directly influences on such phenomena as the formation and the array of unusual nano-size material named quasi-compound, stability of the nano-scale reconstruction, instability of the phase boundary, and array of the binary molecules. It is also shown that the selection of reaction sites is influenced by the weak interaction for coming in molecules, and it is deduced that such weak interaction may relate to the pre-exponential factor (σ) of σe−ε/kT. Taking these facts into account, we could say that it is difficult to predict highly active and highly selective catalyst by potential energy calculation because specific nature of heterogeneous catalysis depends on the σ.