Biomedical subjects

Hideaki Umeyama

Publications and source records attributed to Hideaki Umeyama.

9 recordsLinked to original sources

PubMed2003

Evaluation of the third solvent clusters fitting procedure for the prediction of protein-protein interactions based on the results at the CAPRI blind docking study.

To predict protein-protein interactions, rough or coarse handling for the induced fit problem is proposed. Our method involves the overlap of two hydrophobic interactions as "third solvent clusters fitting." Predictions for binding sites and geometric centers were acceptable, but those of the binding axes were poor. In this study, only the largest benzene cluster was used for the third solvent clusters fitting. For the next CAPRI targets, we must perform protein-protein interaction analyses, which include other smaller benzene clusters.

Benzene↗

PubMed2003

Enlarged FAMSBASE: protein 3D structure models of genome sequences for 41 species.

Enlarged FAMSBASE is a relational database of comparative protein structure models for the whole genome of 41 species, presented in the GTOP database. The models are calculated by Full Automatic Modeling System (FAMS). Enlarged FAMSBASE provides a wide range of query keys, such as name of ORF (open reading frame), ORF keywords, Protein Data Bank (PDB) ID, PDB heterogen atoms and sequence similarity. Heterogen atoms in PDB include cofactors, ligands and other factors that interact with proteins, and are a good starting point for analyzing interactions between proteins and other molecules. The data may also work as a template for drug design. The present number of ORFs with protein 3D models in FAMSBASE is 183 805, and the database includes an average of three models for each ORF. FAMSBASE is available at http://famsbase.bio.nagoya-u.ac.jp/famsbase/.

Animals↗

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

Motion of an antiviral compound in a rhinovirus capsid under rotational symmetry boundary conditions.

A molecular dynamics (MD) simulation of a complex of a rhinovirus protein shell referred to as a "capsid" and an anti-rhinovirus drug, WIN52084s, was performed under the rotational symmetry boundary conditions. For the simulation, the energy parameters of WIN52084s in all-atom approximations were determined by ab initio calculations using a 6-31G* basis set and the two-conformational two-stage restricted electrostatic potential fit method. The motion of WIN52084s and the capsid was focused on in the analysis of the trajectory of the simulation. The root mean square deviations of WIN52084s from the X-ray structure were decomposed to conformational, translational, and rotational components. The translation was further decomposed to radial, longitudinal, and lateral components. The conformation of WIN52084s was rigid, but moving in the pocket. The easiest path of motion for WlN52084s was on the longitudinal line, providing a track for the binding process required of the anti-rhinovirus drug to enter the pocket. The conformation of the pocket was also preserved in the simulation, although the position of the pocket in the capsid fluctuated in the lateral and radial directions.

Antiviral Agents↗

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↗

PubMed2002

Substitution of Gly-548 to Ala in the substrate binding pocket of prothrombin Perijá leads to the loss of thrombin proteolytic activity.

Prothrombin Perijá is a dysprothrombin derived from a homozygous patient that manifests low thrombin activity upon activation in a one-stage assay. Purified prothrombin Perijá showed normal appearance on SDS-PAGE. and was cleaved normally to form alpha-thrombin by the prothrombinase complex. The activated form, thrombin Perijá, however, did not show any proteolytic activity towards native substrates, fibrinogen, protein C or various synthetic substrates for alpha-thrombin, but it was able to bind to antithrombin III, although the binding capacity was markedly reduced even in the presence of heparin. Thrombin Perijá showed full reactivity toward a small inhibitor, DFP, indicating that the molecular defect is in the substrate binding site in the thrombin molecule but not in the active site itself. By DNA sequence analysis of the patient prothrombin gene, we identified a G to C mutation at nucleotide 20016 in exon 14, which predicts a Gly-548 to Ala substitution in the prothrombin Perijá molecule. The structural modeling of thrombin Perijá suggests that Ala-548 is located close to the limb of the cavity wall of the substrate binding pocket, and that the methyl group blocks protrusion of the guanidino group of Arg into the cavity. This steric hindrance may well inhibit the access of Arg-containing substrates to the catalytic Ser-525 leading to the loss of proteolytic activity.

Alanine↗

PubMed2002

[Modeling of all genome and database].

We have developed the protein modeling software FAMS (Full automatic protein modeling system), and using the FAMS the proteins coded in the all the genes were modeled. And we developed web browsing software. We had participated in the CAFASP2 contest of the CASP4 which is the competition of the protein structure prediction. We won almost best server in the CAFASP2 which is the contest of full automatic protein modeling. Accordingly the database quality made by using the FAMS program will be very good. The FAMS modeling web service is available in http://physchem.pharm.kitasato-u.ac.jp/. FAMSBASE is seen in the web site of http://famsbase.bio.nagoya-u.ac.jp/.

Databases, Genetic↗