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H Wako

Publications and source records attributed to H Wako.

At least 19 recordsLinked to original sources
PubMed2006

Analyses of simulations of three-dimensional lattice proteins in comparison with a simplified statistical mechanical model of protein folding.

Folding and unfolding simulations of three-dimensional lattice proteins were analyzed using a simplified statistical mechanical model in which their amino acid sequences and native conformations were incorporated explicitly. Using this statistical mechanical model, under the assumption that only interactions between amino acid residues within a local structure in a native state are considered, the partition function of the system can be calculated for a given native conformation without any adjustable parameter. The simulations were carried out for two different native conformations, for each of which two foldable amino acid sequences were considered. The native and non-native contacts between amino acid residues occurring in the simulations were examined in detail and compared with the results derived from the theoretical model. The equilibrium thermodynamic quantities (free energy, enthalpy, entropy, and the probability of each amino acid residue being in the native state) at various temperatures obtained from the simulations and the theoretical model were also examined in order to characterize the folding processes that depend on the native conformations and the amino acid sequences. Finally, the free energy landscapes were discussed based on these analyses.

Amino Acid Sequence↗
PubMed2000

Significance of a two-domain structure in subunits of phycobiliproteins revealed by the normal mode analysis.

Phycobiliproteins are basic building blocks of phycobilisomes, a supra-molecular assembly for the light-capturing function of photosynthesis in cyanobacteria and red algae. One functional form of phycobiliproteins is a trimeric form consisting of three identical units having C(3) symmetry, with each unit composed of two kinds of subunits, the alpha-subunit and beta-subunit. These subunits have similar chain folds and can be divided into either globin-like or X-Y helices domains. We studied the significance of this two-domain structure for their assembled structures and biological function (light-absorption) using a normal mode analysis to investigate dynamic aspects of their three-dimensional structures. We used C-phycocyanin (C-PC) as an example, and focused on the interactions between the two domains. The normal mode analysis was carried out for the following two cases: 1) the whole subunit, including the two domains; and 2) the globin-like domain alone. By comparing the dynamic properties, such as correlative movements between residues and the fluctuations of individual residues, we found that the X-Y helices domain plays an important role not only in the C(3) symmetry assemblies of the subunits in phycobiliproteins, but also in stabilizing the light absorption property by suppressing the fluctuation of the specific Asp residues near the chromophore. Interestingly, the conformation of the X-Y helices domain corresponds to that of a module in pyruvate phosphate dikinase (PPDK). The module in PPDK is involved in the interactions of two domains, just as the X-Y helices domain is involved in the interactions of two subunits. Finally, we discuss the mechanical construction of the C-PC subunits based on the normal mode analysis.

Amino Acid Sequence↗
PubMed1998

Novel method to detect a motif of local structures in different protein conformations.

In order to detect a motif of local structures in different protein conformations, the Delaunay tessellation is applied to protein structures represented by C(alpha) atoms only. By the Delaunay tessellation the interior space of the protein is uniquely divided up into Delaunay tetrahedra whose vertices are the C(alpha) atom positions. Some edges of the tetrahedra are virtual bonds connecting adjacent residues' C(alpha) atoms along the polypeptide chain and others indicate interactions between residues nearest neighbouring in space. The rules are proposed to assign a code, i.e., a string of digits, to each tetrahedron to characterize the local structure constructed by the vertex residues of one relevant tetrahedron and four surrounding it. Many sets comprised of the local structures with the same code are obtained from 293 proteins, each of which has relatively low sequence similarity with the others. The local structures in each set are similar enough to each other to represent a motif. Some of them are parts of secondary or supersecondary structures, and others are irregular, but definite structures. The method proposed here can find motifs of local structures in the Protein Data Bank much more easily and rapidly than other conventional methods, because they are represented by codes. The motifs detected in this method can provide more detailed information about specific interactions between residues in the local structures, because the edges of the Delaunay tetrahedra are regarded to express interactions between residues nearest neighbouring in space.

Models, Molecular↗
PubMed1996

A comparative study of dynamic structures between phage 434 Cro and repressor proteins by normal mode analysis.

Two DNA binding proteins, Cro and the amino-terminal domain of the repressor of bacteriophage 434 (434 Cro and 434 repressor) that regulate gene expression and contain a helix-turn-helix (HTH) motif responsible for their site-specific DNA recognition adopt very similar three-dimensional structures when compared to each other. To reveal structural differences between these two similar proteins, their dynamic structures, as examined by normal mode analysis, are compared in this paper. Two kinds of structural data, one for the monomer and the other for a complex with DNA, for each protein, are used in the analyses. From a comparison between the monomers it is found that the interactions of Ala-24 in 434 Cro or Val-24 in 434 repressor, both located in the HTH motif, with residues 44, 47, 48, and 51 located in the domain facing the motif, and the interactions between residues 17, 18, 28, and 32, located in the HTH motif, cause significant differences in the correlative motions of these residues. From the comparison between the monomer and the complex with DNA for each protein, it was found that the first helix in the HTH motif is distorted in the complex form. While the residues in the HTH motif in 434 Cro have relatively larger positive correlation coefficients of motions with other residues within the HTH motif, such correlations are not large in the HTH motif of 434 repressor. It is suggestive to their specificity because the 434 repressor is less specific than 434 Cro. Although a structural comparison of proteins has been performed mainly from a static or geometrical point of view, this study demonstrates that the comparison from a dynamic point of view, using the normal mode analysis, is useful and convenient to explore a difference that is difficult to find only from a geometrical point of view, especially for proteins very similar in structure.

Amino Acid Sequence↗
PubMed1995

Secondary structure prediction of beta-subunits of the gonadotropin-thyrotropin family from its aligned sequences using environment-dependent amino-acid substitution tables and conformational propensities.

The secondary structures of beta-subunits of the glycoprotein hormone family, LH (luteinizing hormone), CG (chorionic gonadotropin), FSH (follicle stimulating hormone), TSH (thyroid stimulating hormone), and GTH I/GTH II (two types of fish gonadotropins), are predicted by comparing an amino-acid substitution pattern at equivalent sites in their aligned sequences with environment-dependent amino-acid substitution tables and conformational propensities calculated from other protein families whose three-dimensional structures are known. According to the prediction results, together with other structural information obtained from experiments, the following points come up as important structural features of the beta-subunits of this family; The regions assigned to regular secondary structures (one alpha-helix and three beta-strands) are considered to constitute a core of the beta-subunits. They involve interaction sites with carbohydrate and alpha-subunit. Out of the six disulfide bonds formed in the beta-subunit, four are located together on one side of the core, and the other two on the opposite side. The two regions assumed to be a receptor binding region from experiments (therefore, species-specific regions) are predicted as loops located on the same side of the beta-subunit in this study. Some of the predicted loops are rich in proline residues. While the positions of proline residues are conserved in the family generally, there are hormone- or species-specific ones in the loop that is assumed to take part in receptor binding. The possible importance of proline residues in hormone or species specificity is discussed. (After submitting the manuscript the X-ray crystal structure of human CG was published. In order to evaluate the prediction, the original manuscript is kept intact and a comparison has been made between the prediction results and the crystal structure in an appendix).

Amino Acid Sequence↗
PubMed1994

The recognition of protein structure and function from sequence: adding value to genome data.

The explosion of DNA sequence data from genome projects presents many challenges. For instance, we must extend our current knowledge of protein structure and function so that it can be applied to these new sequences. The derivation of rules for the relationships between sequence and structure allow us to recognize a common fold by the use of tertiary templates. New techniques enable us to begin to meet the challenge of rule-based modelling of distantly related proteins. This paper describes an integrated and knowledge-based approach to the prediction of protein structure and function which can maximize the value of sequence information.

Amino Acid Sequence↗
PubMed1994

Use of amino acid environment-dependent substitution tables and conformational propensities in structure prediction from aligned sequences of homologous proteins. I. Solvent accessibility classes.

Buried and exposed residues are predicted by composing amino acid substitution patterns and mean propensities for the two solvent accessibility classes with the amino acid residues at equivalent sites in aligned sequences of homologous proteins. In a study of 13 protein families, the accuracy of the prediction is around 77% (the correlation coefficient between the predicted and observed accessibility classes is 0.52). The environment dependent amino acid substitution tables are especially important in prediction of buried hydrophilic and exposed hydrophobic residues, which are not well predicted with propensities alone. Since the prediction is site-specific in the sense that any averaged properties over neighbouring residues are not required, the results can be used for the prediction of secondary structures by detecting periodicity in the sequence of buried and exposed classes.

Amino Acid Sequence↗
PubMed1994

Use of amino acid environment-dependent substitution tables and conformational propensities in structure prediction from aligned sequences of homologous proteins. II. Secondary structures.

A three-step method is presented to predict secondary structures of proteins, by utilizing aligned sequences of homologous proteins. Mean propensities and amino acid substitution patterns at a given site in the aligned sequences are first evaluated for four conformational states (i.e. alpha-helix, beta-strand, buried coil and exposed coil). Capping rules are applied in order to define boundaries of the secondary-structure segments more precisely. In the second step beta-strand is predicted by searching regions predicted as coil for the two patterns characteristic of alternating and fully buried beta-strands. The complete sequences of the solvent-accessibility classes predicted by substitution tables and propensities are also searched using Fourier transform methods for alpha-helical periodicity. After applying capping rules, the alpha-helices and beta-strands predicted in the second step replace, where appropriate, the conformational states predicted in the first step. Finally, in the third step, if one of the four conformational states is assigned to the residues at an equivalent site of aligned sequences in more than a given fraction of the proteins, such a state is reassigned to all the residues at that site. The method is applied to 13 protein families, which contain four folding types, alpha, beta, alpha/beta and alpha + beta. The accuracy of the prediction ranges from 60 to 79% (mean percentage over the 13 families is 69%). For comparison the Garnier-Osguthorpe-Robson (GOR) method is also applied to them. Although the mean prediction accuracy for the GOR method, 58%, can be improved to 63% by applying the second and third steps in this method, there remain four families with less than 55% accuracy. The mean accuracy is relatively higher and poor predictions are reduced in this method.

Amino Acid Sequence↗
PubMed1991

Distance-constraint approach to higher-order structures of globular proteins with empirically determined distances between amino acid residues.

An analysis of higher-order structures of globular proteins by means of a distance-constraint approach is presented. Conformations are generated for each of 21 test proteins of small and medium sizes by optimizing an objective function f = sigma sigma wij(dij - (dij]2, where dij is a distance between residues i and j in a calculated conformation, (dij) is an assigned distance to the (ij) pair of residues which is determined based on the statistics of known three-dimensional structures of 14 proteins in the earlier study, and wij is a weighting factor. (dij) involves information about hydrophobicity and hydrophilicity of each amino acid residue and about connectivity of a polypeptide chain. In these calculations, only the amino acid sequence is used as input data specific to a calculated protein. With respect to higher-order structures regenerated in the optimized conformations, the following properties are analyzed: (a) N14 of a residue, defined as the number of residues surrounding the residue located within a sphere of radius of 14 A; (b) root-mean-square differences of the global and local conformations from the corresponding X-ray conformations; (c) distance profiles in the short and medium ranges; and (d) distance maps. The effects of supplementary information about locations of secondary structures and disulfide bonds are also examined to discuss the potential ability of this methodology to predict the three-dimensional structures of globular proteins.

Amino Acids↗
PubMed1989

Monte Carlo simulations of a protein molecule with and without hydration energy calculated by the hydration-shell model.

Monte Carlo simulations of a small protein, crambin, were carried out with and without hydration energy. The methodology presented here is characterized, as compared with the other similar simulations of proteins in solution, by two points: (1) protein conformations are treated in fixed geometry so that dihedral angles are independent variables rather than cartesian coordinates of atoms; and (2) instead of treating water molecules explicitly in the calculation, hydration energy is incorporated in the conformational energy function in the form of sigma giAi, where Ai is the accessible surface area of an atomic group i in a given conformation, and gi is the free energy of hydration per unit surface area of the atomic group (i.e., hydration-shell model). Reality of this model was tested by carrying out Monte Carlo simulations for the two kinds of starting conformations, native and unfolded ones, and in the two kinds of systems, in vacuo and solution. In the simulations starting from the native conformation, the differences between the mean properties in vacuo and solution simulations are not very large, but their fluctuations around the mean conformation during the simulation are relatively smaller in solution than in vacuo. On the other hand, in the simulations starting from the unfolded conformation, the molecule fluctuates much more largely in solution than in vacuo, and the effects of taking into account the hydration energy are pronounced very much. The results suggest that the method presented in this paper is useful for the simulations of proteins in solution.

Chemical Phenomena↗
PubMed1989

Dynamic structures of globular proteins with respect to correlative movements of residues calculated in the normal mode analysis.

Dynamic structures of globular proteins are studied on the basis of correlative movements of residues around their native conformations, which are computed by means of the normal mode analysis. To describe the dynamic structures of a protein, the core regions moving with strong positive or negative correlations to other regions of the polypeptide chain are detected from the correlation maps of the movements of residues. Such core regions are different, according to the definition, from the regions defined from a geometrical point of view, such as secondary structures, domains, modules, and so on. The core regions are actually detected for four proteins, myoglobin, Bence-Jones protein, flavodoxin, and hen egg-white lysozyme, with different folding types from each other. The results show that some of them coincide with the secondary structures, domains, or modules, but others do not. Then, the dynamic structure of each protein is discussed in terms of the dynamic cores detected, as compared with the secondary structures, domains, and modules.

Bence Jones Protein↗
PubMed1989

Inspection of three-dimensional structures of proteins with dynamical information from the normal mode analysis.

In this paper it is demonstrated that, to analyze structural data of proteins obtained from X-ray crystallography, the normal mode analysis in dihedral angle space can serve to supplement X-ray data as a useful system for gaining information on their dynamical as well as static structures. Especially, the following two subjects are discussed; first, the breakdown of the motions of a limited region in a polypeptide chain (e.g., an alpha-helix, a beta-strand or a loop) into internal and external motions reveals whether the region is flexible, or it is rigid but mobile when it has large fluctuations. Second, the correlation map between atomic motions serves to provide information for dividing the chain into segments, such as domains or modules, from a dynamical rather than from a geometrical point of view. It is shown that the modules proposed by M. Go appear distinctly in the correlation map as the regions in which clusters of atoms with positive correlation coefficients of their movements to each other exist. Furthermore, the modules are characterized by the negative correlation coefficients of the movements of the atoms in the clusters in a particular module to such movements in a different module.

Computer Simulation↗
PubMed1984

Monte Carlo study on local and small-amplitude conformational fluctuation in hen egg white lysozyme.

Local and small-amplitude conformational fluctuations in hen egg white lysozyme around its native conformation were studied by the Monte Carlo simulation with conformational energy calculation. In order to carry out such a simulation in a shorter computation time, the following method was devised: at each step of the simulation a segment of consecutive four residues, say, i to i + 3, is chosen at random from N residues and then the small conformational change of the segment is performed so that the conformations of the two blocks of residues 1 to i - 1 and i + 4 to N as well as the mutual location of the two blocks are not changed. In this simulation it was found that calculated atomic displacements and fluctuations of dihedral angles well reflect the characteristics of local conformations, for example, stiffness of regular secondary structures and flexibility of non-regular structures, especially of the regions around the lips of the active-site cleft and of the region that undergoes conformational change on ligand binding to the active site. The flexibility of these regions is probably necessary for the reaction of the active site to the ligand. A close correlation between the solvent accessibility of the side chain of each residue and its flexibility was also observed. Furthermore, it was shown that the results obtained in this study are in a good agreement with the same properties observed in analyzing temperature factors derived from refinement of X-ray data of the protein.

Animals↗
PubMed1984

Unfolding of tertiary structures of proteins.

The unfolding pathway of lysozyme was investigated by carrying out the computer simulation. Taking into account the simultaneous change of both the dihedral angels phi and psi of a residue, we explore the detailed features of the conformational energy profiles. The triangle distance map shows that the lysozyme molecule is divided into three domains, 1-40, 41-101 and 102-129 in amino acid residue numbers (referred to as the domains I, II and III, respectively). The calculated unfolding process indicates that in the early stage of unfolding domain III located at the C-terminal begins to be detached from the other two, and then domain I can be unfolded. The long-range interactions between domains I and III stabilize the whole molecule and give the cooperative nature of the folding. The calculated unfolding pathway of lysozyme is consistent with the folding pathway proposed by Anderson & Wetlaufer [J. Biol. Chem. (1976). 251, 3147-3153] who identified the disulfide bondings in the early stage of the glutathione regeneration. A simplified treatment of unfolding for myoglobin is also discussed in the Appendix.

Muramidase↗
PubMed1976

Tertiary structures of gastrin-like tetrapeptides.

Tertiary structures of gastrin-like tetrapeptide Trp-Met-Asp-Phe-NH2 and those substituted by Leu, Val or Gly for Met are studied. The lowest energy conformations of the side chains when the back bone is fixed in alpha-helix are obtained by modified minimization algorithm. It is suggested that protein folding proceeds in the accessible conformation space as a self-organization process leading to minimum energy conformation in this space.

Aspartic Acid↗
PubMed1975

[Artificial nursing of new-born cynomolgus monkeys as a model of the human infant and development of abnormal behavior (author's transl)].

New-born cynomolgus monkeys were sucessfully reared by artificial nursing that was started just afterbirth with a 12% solution of a commercially prepared powdered-milk (Yukijirushi, P 7a) containing 13.3g of protein per 100g. Marked growth-retardation was observed in baby cynomolgus monkeys fed on a 12% solution of the modified P 7a milk containing only 6.6g of protein per 100g to which lactose was supplemented to give a baby monkey the same caloric value as that of the original P 7a milk. These artificially reared cynomolgus monkeys manifested various kinds of abnormal behavior such as self-clasping, autism-like self mouthing, huddling, stereotype rocking, head-knocking, autoerotism, fear, aggression, etc.. Generally, development of these abnormal behaviors was more noticeable in the monkeys nursed with a milk bottle fixed to the side of a cage without human contact than in the monkeys nursed by a care-taker with bodily touching. These qualitative observational results indicate that the new-born cynomolgus monkey can be used as a model of the human baby for research into the relationship between malnutrition and abnormal physical and mental growth.

Animal Nutritional Physiological Phenomena↗