Biomedical subjects

Kenshu Kamiya

Publications and source records attributed to Kenshu Kamiya.

4 recordsLinked to original sources

PubMed2003

Algorithm for normal mode analysis with general internal coordinates.

A technique for performing normal vibrational analysis for biological macromolecules using general internal coordinates is proposed. The technique is based on the conventional algorithm for calculating the second derivatives of potential and kinetic energies using intramolecular dihedral angles, intermolecular translation, and rotation as variables [Braun, W. et al., J Phys Soc Jpn 1984, 53, 3269]. We extend the algorithm to include more general internal coordinates, bond stretching, angle bending, and so forth, without assuming two-body interactions. The essential point is the separation of the variables for potential functions and vibrational analysis. With our technique, we can arbitrarily choose any combination of internal coordinates as variables, free from the functional form of potential energy. We can analyze complex systems such as a multiple molecular system including solvents or a transition state of chemical reactions. In addition, mixed use of the potentials of molecular mechanics and quantum chemistry is possible.

Journal Article↗

PubMed2003

Dynamic character of human growth hormone and its receptor: normal mode analysis.

Human growth hormone (hGH) induces dimerization of its binding protein (hGHbp). hGH binds to the first hGHbp (bp1) on site 1, and then the hGH-bp1 heterodimer complex binds to the second hGHbp (bp2) on site 2. Although the interactions of hGH and hGHbps have been studied from different viewpoints, few studies from a dynamic viewpoint have been reported. Especially, since in the SCOP domain database hGHbp is classified as two clear immunoglobulin-like domains, it is of interest to understand how hGH interacts with the hGHbp domains. Therefore, we carried out normal mode analysis (NMA) of free hGH, free bp1, free bp2, and the hGH-bp1 heterodimer complex, as well as the hGH-bp1-bp2 ternary complex to investigate how the dynamics of the proteins change before and after forming the complexes. NMA showed that the domain motion between the N-terminal and the C-terminal domains of free bp1 markedly decreased after binding to hGH, and that the domain motion of bp2 decreased similarly after binding to the hGH-bp1 heterodimer complex. The present study demonstrates that hGH regulates the inter-domain motions of both hGHbps.

Human Growth Hormone↗

PubMed2003

Dynamic flexibility of a peptide-binding groove of human HLA-DR1 class II MHC molecules: normal mode analysis of the antigen peptide-class II MHC complex.

Class II major histocompatibility complex (MHC) has tolerance for binding longer antigen peptides than those bound by class I MHC. In this paper, a normal mode analysis on HLA-DR1 class II MHC involving an antigen peptide indicated that the peptide-binding groove had some different dynamic characteristics from that of HLA-A2 class I MHC. The dynamic changes in the class I groove with removal of the bound peptide were limited primarily to the central region and the C-terminal side (corresponding to the C-terminal side of the bound peptide) of the groove, while the dynamic changes in the class II groove with removal of the bound peptide extended to the whole of the groove, and were especially remarkable around a strand located in the N-terminal side (corresponding to the N-terminal side of the bound peptide) of the groove. These results suggest that the N-terminal side of the class II groove is more flexible than the same side of the class I groove, and this flexibility may allow some N-terminal residues of the bound peptide to extend outside the class II groove. Definite anti-correlative motions with removal of the bound peptide appeared between two alpha-helical regions of class II MHC as in the case of class I MHC. These motions of the class II groove may play an important role in obtaining "a flexible dynamic fit" against diverse longer peptides both of whose terminals extend outside the groove.

Binding Sites↗

PubMed2002

Dynamic characteristics of a peptide-binding groove of human HLA-A2 class I MHC molecules: normal mode analysis of the antigen peptide-class I MHC complex.

Class I major histocompatibility complex (MHC) binds antigen peptides with various sequences. We performed a normal mode analysis of HLA-A2 MHC that binds three peptides with different affinity. HLA-A2 MHC has a peptide-binding groove composed of two alpha-helices (residue 49-84, residue 140-179). Some residues in the center of the groove showed an increase in fluctuations and some residue pairs between two helix groups showed a negative change in correlations by removing the antigen peptide. The extent of the fluctuation and correlation changes correlated well with the experimental ranking of the three peptides in binding affinity. Some definite anti-correlative motions were found between two helix groups in low frequency modes (<50 cm(-1)) by removing the antigen peptide. We propose that the above anti-correlative motions play an important role to bind the antigen peptide, especially in obtaining a "dynamic fit."

Crystallography, X-Ray↗