To raise the accuracy of the force field for nucleic acids, several parameters were elaborated, focusing on the rotation around chi torsion axis. The reliability of molecular dynamics (MD) simulation was significantly increased by improving the torsion parameters at C8--N9--C1'--X (X = H1', C2', O4') in A, G and those at C6--N1--C1'--X in C, T, and U. In this work, we constructed small models representing the chemical structure of A, G, C, T, and U, and estimated energy profile for chi-axis rotation by executing numerous quantum mechanical (QM) calculations. The parameters were derived by discrete Fourier transformation of the calculated QM data. A comparison in energy profile between molecular mechanical (MM) calculation and QM one shows that our presently derived parameters well reproduce the energy surface of QM calculation for all the above torsion terms. Furthermore, our parameters show a good performance in MD simulations of some nucleic acids. Hence, the present refinement of parameters will enable us to perform more accurate simulations for various types of nucleic acids.

Major histocompatibility complex (MHC) is a transmembrane glycoprotein that plays an important role in immunological system. Human MHC molecule is usually called as human leukocyte antigen (HLA) and HLA molecules are grouped into class I and II. MHC class I molecule is a heterodimer of heavy chain called a chain, whose mass-weight is 45 kDa, and light chain called b2 micro globulin (b2m) with a mass-weight of 12 kDa. A complex of an HLA and a peptide derived from antigen is displayed on the surface of nucleated cell or platelet. HLA heavy chain has a quite large diversity and thousands of genes have been detected so far, and the number of known genes for HLA heavy chain is still increasing. Each individual has two or three kinds of HLA out of several thousands of HLA genes.Viral protein or cancer-related antigens are detected as foreign molecules in a cell and dissociated by proteasome into peptide fragments consisting of 6-15 amino residues.1) This peptide fragment is bound to HLA class I molecule and the complex is carried to the cell surface in antigen display cells. Cytotoxic T lymphocytes (CTL) expressing T cell receptor recognize the complex, which results in inducing the immunological response to attack the virus-infected or oncogenic cells to exclude virus or tumor. 2)Immunological response has attracted much recent attention because of its potential for immunotherapy. At present, several peptides are assumed to be effective for medical treatment of cancer, leukemia, hepatitis C, and applied to patients in a clinical trial as vaccine through the controlled vaccination.3-5) This peptide-vaccine therapy is expected to lead the regression of disease-related cells without damaging normal tissues. Since the combination of HLA genes has a large diversity, the selection of peptide adequate for each individual is one of the important issues to enhance the performance of immunotherapy.The discovery of a peptide inducing strong immunological response is a key factor in immunotherapy. Since the peptide firmly bound to HLA molecule will be effective as medical material, the search of potent peptide, usually called as epitope, is critically important. In this study, we focus on Wilms' tumor (WT1) protein.6) WT1 protein is encoded in b2 Wilms' tumor gene and overexpressed in leukemic and solid tumor cell. A 9-mer amino acid peptide encoded in WT1 protein was already known to work as an antigenic peptide for HLA-A*2402 molecule. Oka and his co-workers reported the experimental findings that the replacement of the second amino acid residue, which is considered to be deeply responsible for the peptide binding to HLA-A*2402, induced strong immunological response of WT1 specific CTLs compared to the natural peptide. A peptide containing a single amino residue mutation is currently applies for the clinical trial for a vaccination against solid tumor or leukemia. 7)Computer simulation enables us to visualize the interaction of proteins or the interaction of a chemical compound and its target protein. Molecular dynamics (MD) ...

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