著者
Masami Ikeda Minoru Sugihara Makiko Suwa
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.15, pp.104-110, 2018 (Released:2018-04-27)
参考文献数
28
被引用文献数
3

We report the development of the SEVENS database, which contains information on G-protein coupled receptor (GPCR) genes that are identified with high confidence levels (A, B, C, and D) from various eukaryotic genomes, by using a pipeline comprising bioinformatics softwares, including a gene finder, a sequence alignment tool, a motif and domain assignment tool, and a transmembrane helix predictor.SEVENS compiles detailed information on GPCR genes, such as chromosomal mapping position, phylogenetic tree, sequence similarity to known genes, and protein function described by motif/domain and transmembrane helices. They are presented in a user-friendly interface. Because of the comprehensive gene findings from genomes, SEVENS contains a larger data set than that of previous databases and enables the performance of a genome-scale overview of all the GPCR genes. We surveyed the complete genomes of 68 eukaryotes, and found that there were between 6 and 3,470 GPCR genes for each genome (Level A data). Within these genes, the number of receptors for various molecules, including biological amines, peptides, and lipids, were conserved in mammals, birds, and fishes, whereas the numbers of odorant receptors and pheromone receptors were highly diverse in mammals. SEVENS is freely available at http://sevens.cbrc.jp or http://sevens.chem.aoyama.ac.jp.
著者
Nobuhiro Go
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.16, pp.256-263, 2019 (Released:2019-11-29)
参考文献数
11

The snake cube puzzle made of a linear array of 27 cubes and its modified and extended versions are used as theoretical models to study the mechanism of folding of proteins into their sequence-specific native three-dimensional structures. Each of the three versions is characterized by the respective set of characteristics attributed to each of its constituent cubes and an array is characterized by its specific sequence of the cube characteristics. The aim of the puzzles is to fold the cube array into a compact 3×3×3 cubic structure. In all three versions, out of all possible sequences, only a limited fraction of sequences are found foldable into the compact cube. Even among foldable sequences, the structures folded into the compact 3×3×3 cube are found often not uniquely determined from the sequence. By comparing the results obtained for the three versions of models, we conclude that the power of the hydrophobic interactions to make the folded structure unique to the sequence is much weaker than the geometrical varieties of constituent cubes as modelled in the original snake cube puzzle. However, when this weak cube attribute is compounded to that of the original snake cube puzzle, the power is enhanced very effectively. This is a strong manifestation of the consistency principle: The sequence-specific native structure of protein is realized as a result of consistency of various types of interactions working in protein.
著者
Takayoshi Tomono Hisao Kojima Satoshi Fukuchi Yukako Tohsato Masahiro Ito
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.12, pp.57-68, 2015 (Released:2015-11-12)
参考文献数
59
被引用文献数
2

Glycans play important roles in such cell-cell interactions as signaling and adhesion, including processes involved in pathogenic infections, cancers, and neurological diseases. Glycans are biosynthesized by multiple glycosyltransferases (GTs), which function sequentially. Excluding mucin-type O-glycosylation, the non-reducing terminus of glycans is biosynthesized in the Golgi apparatus after the reducing terminus is biosynthesized in the ER. In the present study, we performed genome-wide analyses of human GTs by investigating the degree of conservation of homologues in other organisms, as well as by elucidating the phylogenetic relationship between cephalochordates and urochordates, which has long been controversial in deuterostome phylogeny. We analyzed 173 human GTs and functionally linked glycan synthesis enzymes by phylogenetic profiling and clustering, compiled orthologous genes from the genomes of other organisms, and converted them into a binary sequence based on the presence (1) or absence (0) of orthologous genes in the genomes. Our results suggest that the non-reducing terminus of glycans is biosynthesized by newly evolved GTs. According to our analysis, the phylogenetic profiles of GTs resemble the phylogenetic tree of life, where deuterostomes, metazoans, and eukaryotes are resolved into separate branches. Lineage-specific GTs appear to play essential roles in the divergence of these particular lineages. We suggest that urochordates lose several genes that are conserved among metazoans, such as those expressing sialyltransferases, and that the Golgi apparatus acquires the ability to synthesize glycans after the ER acquires this function.
著者
Fumio Oosawa
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.15, pp.151-158, 2018 (Released:2018-07-18)
参考文献数
42
被引用文献数
1

An enormous amount of research has been performed to characterize actin dynamics. Structural biology investigations have determined the localization of main chains and their changes coupled with G (Globular)-F (Filamentous) transformation of actin, whereas local thermal fluctuations that may be caused by free rotations of the tips of side chains are not yet fully investigated. This paper argues if the entropy change of actin accompanied by the G-F transformation is simply attributable to the changes in hydration. It took almost 10 years to understand that the actin filament is semi-flexible. This flexibility was visually confirmed as the development of optical microscope techniques, and the direct observation of actin severing events in the presence of actin binding proteins became possible. Finally, I expect the deep understanding of actin dynamics will lead to the elucidation of self-assembly mechanisms of the living creature.
著者
Tatsuya Okuno Koya Kato Shintaro Minami Tomoki P. Terada Masaki Sasai George Chikenji
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.149-156, 2016 (Released:2016-07-14)
参考文献数
31
被引用文献数
3

We discuss methods and ideas of virtual screening (VS) for drug discovery by examining the performance of VS-APPLE, a recently developed VS method, which extensively utilizes the tendency of single binding pockets to bind diversely different ligands, i.e. promiscuity of binding pockets. In VS-APPLE, multiple ligands bound to a pocket are spatially arranged by maximizing structural overlap of the protein while keeping their relative position and orientation with respect to the pocket surface, which are then combined into a multiple-ligand template for screening test compounds. To greatly reduce the computational cost, comparison of test compound structures are made only with limited regions of the multiple-ligand template. Even when we use the narrow regions with most densely populated atoms for the comparison, VS-APPLE outperforms other conventional VS methods in terms of Area Under the Curve (AUC) measure. This region with densely populated atoms corresponds to the consensus region among multiple ligands. It is typically observed that expansion of the sampled region including more atoms improves screening efficiency. However, for some target proteins, considering only a small consensus region is enough for the effective screening of test compounds. These results suggest that the performance test of VS methods sheds light on the mechanisms of protein-ligand interactions, and elucidation of the protein-ligand interactions should further help improvement of VS methods.
著者
Nobuyuki Uchikoga Yuri Matsuzaki Masahito Ohue Yutaka Akiyama
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.105-115, 2016 (Released:2016-07-14)
参考文献数
31
被引用文献数
6

Analysis of protein-protein interaction networks has revealed the presence of proteins with multiple inter­action ligand proteins, such as hub proteins. For such proteins, multiple ligands would be predicted as interacting partners when predicting all-to-all protein-protein interactions (PPIs). In this work, to obtain a better understanding of PPI mechanisms, we focused on protein interaction surfaces, which differ between protein pairs. We then performed rigid-body docking to obtain information of interfaces of a set of decoy structures, which include many possible interaction surfaces between a certain protein pair. Then, we investigated the specificity of sets of decoy interactions between true binding partners in each case of alpha-chymotrypsin, actin, and cyclin-dependent kinase 2 as test proteins having mul­tiple true binding partners. To observe differences in interaction surfaces of docking decoys, we introduced broad interaction profiles (BIPs), generated by assembling interaction profiles of decoys for each protein pair. After cluster analysis, the specificity of BIPs of true binding partners was observed for each receptor. We used two types of BIPs: those involved in amino acid sequences (BIP-seqs) and those involved in the compositions of interacting amino acid residue pairs (BIP-AAs). The specificity of a BIP was defined as the number of group members including all true binding partners. We found that BIP-AA cases were more specific than BIP-seq cases. These results indicated that the composition of inter­acting amino acid residue pairs was sufficient for determining the properties of protein interaction surfaces.
著者
Go Watanabe Daisuke Nakajima Akinori Hiroshima Haruo Suzuki Shigetaka Yoneda
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.12, pp.131-138, 2015 (Released:2015-12-22)
参考文献数
29
被引用文献数
1

A precise 100-ns molecular dynamics simulation in aquo was performed for the heterotetrameric sarcosine oxidase bound with a substrate analogue, dimethylglycine. The spatial region including the protein was divided into small rectangular cells. The average number of the water molecules locating within each cell was calculated based on the simulation trajectory. The clusters of the cells filled with water molecules were used to determine the water channels. The narrowness of the channels, the average hydropathy indices of the residues of the channels, and the number of migration events of water molecules through the channels were consistent with the selective transport hypothesis whereby tunnel T3 is the pathway for the exit of the iminium intermediate of the enzyme reaction.
著者
Masaaki Kotera Susumu Goto
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.195-205, 2016 (Released:2016-07-15)
参考文献数
86
被引用文献数
5

Metabolic pathway reconstruction presents a challenge for understanding metabolic pathways in organisms of interest. Different strategies, i.e., reference-based vs. de novo, must be used for pathway reconstruction depending on the availability of well-characterized enzymatic reactions. If at least one enzyme is already known to catalyze a reaction, its amino acid sequence can be used as a reference for identifying homologous enzymes in the genome of an organism of interest. Where there is no known enzyme able to catalyze a corresponding reaction, however, the reaction and the corresponding enzyme must be predicted de novo from chemical transformations of the putative substrate-product pair. This review summarizes studies involving reference-based and de novo metabolic pathway reconstruction and discusses the importance of the classification and structure-function relationships of enzymes.
著者
Shumpei Matsuno Masahito Ohue Yutaka Akiyama
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.17, pp.2-13, 2020 (Released:2020-02-07)
参考文献数
30

Protein functions can be predicted based on their three-dimensional structures. However, many multidomain proteins have unstable structures, making it difficult to determine the whole structure in biological experiments. Additionally, multidomain proteins are often decomposed and identified based on their domains, with the structure of each domain often found in public databases. Recent studies have advanced structure prediction methods of multidomain proteins through computational analysis. In existing methods, proteins that serve as templates are used for three-dimensional structure prediction. However, when no protein template is available, the accuracy of the prediction is decreased. This study was conducted to predict the structures of multidomain proteins without the need for whole structure templates.We improved structure prediction methods by performing rigid-body docking from the structure of each domain and reranking a structure closer to the correct structure to have a higher value. In the proposed method, the score for the domain-domain interaction obtained without a structural template of the multidomain protein and score for the three-dimensional structure obtained during docking calculation were newly incorporated into the score function. We successfully predicted the structures of 50 of 55 multidomain proteins examined in the test dataset.Interaction residue pair information of the protein-protein complex interface contributes to domain reorganizations even when a structural template for a multidomain protein cannot be obtained. This approach may be useful for predicting the structures of multidomain proteins with important biochemical functions.
著者
Jean-François Gibrat
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.16, pp.444-451, 2019 (Released:2019-11-29)
参考文献数
13

This paper presents a preliminary work consisting of two contributions. The first one is the design of a very efficient algorithm based on an “Overlap-Layout-Consensus” (OLC) graph to assemble the long reads provided by 3rd generation technologies. The second concerns the analysis of this graph using algebraic topology concepts to determine, in advance, whether the assembly of the genome will be straightforward, i.e., whether it will lead to a pseudo-Hamiltonian path or cycle, or whether the results will need to be scrutinized. In the latter case, it will be necessary to look for “loops” in the OLC assembly graph caused by unresolved repeated genomic regions, and then try to untie the “knots” created by these regions.
著者
Keiichi Kojima Hiroshi C. Watanabe Satoko Doi Natsuki Miyoshi Misaki Kato Hiroshi Ishikita Yuki Sudo
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.15, pp.179-188, 2018 (Released:2018-09-07)
参考文献数
42
被引用文献数
2

Anion channelrhodopsin-2 (ACR2), a light-gated channel recently identified from the cryptophyte alga Guillardia theta, exhibits anion channel activity with exclusive selectivity. In addition to its novel function, ACR2 has become a focus of interest as a powerful tool for optogenetics. Here we combined experimental and computational approaches to investigate the roles of conserved carboxylates on the anion transport activity of ACR2 in Escherichia coli membrane. First, we replaced six conserved carboxylates with a neutral residue (i.e. E9Q, E56Q, E64Q, E159Q, E219Q and D230N), and measured anion transport activity using E. coli expression system. E159Q and D230N exhibited significantly lower anion transport activity compared with wild-type ACR2 (1/12~1/3.4), which suggests that E159 and D230 play important roles in the anion transport. Second, to explain its molecular aspects, we constructed a homology model of ACR2 based on the crystal structure of a cation channelrhodopsin (ChR). The model structure showed a cavity formed by four transmembrane helices (TM1, TM2, TM3 and TM7) similar to ChRs, as a putative anion conducting pathway. Although E159 is not located in the putative pathway, the model structure showed hydrogen bonds between E159 and R129 with a water molecule. D230 is located in the pathway near the protonated Schiff base (PSB) of the chromophore retinal, which suggests that there is an interaction between D230 and the PSB. Thus, we demonstrated the functional importance and the hypothetical roles of two conserved carboxylates, E159 and D230, in the anion transport activity of ACR2 in E. coli membrane.
著者
Junko Taguchi Akio Kitao
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.117-126, 2016 (Released:2016-07-14)
参考文献数
37
被引用文献数
6

We examine the dynamic features of non-trivial allosteric binding sites to elucidate potential drug binding sites. These allosteric sites were previously found to be allosteric after determination of the protein-drug co-crystal structure. After comprehensive search in the Protein Data Bank, we identify 10 complex structures with allosteric ligands whose structures are very similar to their functional forms. Then, possible pockets on the protein surface are searched as potential ligand binding sites. To mimic ligand binding to the pocket, complex models are generated to fill out each pocket with pseudo ligand blocks consisting of spheres. Normal mode analysis of the elastic network model is performed for the complex models and unbound structures to assess the change of protein dynamics induced by ligand binding. We examine nine profiles to describe the dynamic and positional characteristics of the pockets, and identify the change of fluctuation around the ligand, ΔMSFbs, as the best profile for distinguishing the allosteric sites from the other sites in 8 structures. These cases should be considered as examples of dynamics-driven allostery, which accompanies significant changes in protein dynamics. ΔMSFbs is suggested to be used for the search of potential dynamics-driven allosteric sites in proteins for drug discovery.
著者
Akihiro Okamoto Yoshihide Tokunou Junki Saito
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.71-76, 2016 (Released:2016-05-27)
参考文献数
32
被引用文献数
8

Outer-membrane c-type cytochrome (OM c-Cyt) complexes in several genera of iron-reducing bacteria, such as Shewanella and Geobacter, are capable of transporting electrons from the cell interior to extracellular solids as a terminal step of anaerobic respiration. The kinetics of this electron transport has implications for controlling the rate of microbial electron transport during bioenergy or biochemical production, iron corrosion, and natural mineral cycling. Herein, we review the findings from in-vivo and in-vitro studies examining electron transport kinetics through single OM c-Cyt complexes in Shewanella oneidensis MR-1. In-vitro electron flux via a purified OM c-Cyt complex, comprised of MtrA, B, and C proteins from S. oneidensis MR-1, embedded in a proteoliposome system is reported to be 10- to 100-fold faster compared with in-vivo estimates based on measurements of electron flux per cell and OM c-Cyts density. As the proteoliposome system is estimated to have 10-fold higher cation flux via potassium channels than electrons, we speculate that the slower rate of electron-coupled cation transport across the OM is responsible for the significantly lower electron transport rate that is observed in-vivo. As most studies to date have primarily focused on the energetics or kinetics of interheme electron hopping in OM c-Cyts in this microbial electron transport mechanism, the proposed model involving cation transport provides new insight into the rate detemining step of EET, as well as the role of self-secreted flavin molecules bound to OM c-Cyt and proton management for energy conservation and production in S. oneidensis MR-1.
著者
Yasumasa Joti Akio Kitao
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.16, pp.240-247, 2019 (Released:2019-11-29)
参考文献数
28

Terahertz time-domain spectra (THz-TDS) were investigated using the results of molecular dynamics (MD) simulations of Staphylococcal nuclease at two hydration states in the temperature range between 100 and 300 K. The temperature dependence of THz-TDS was found to differ significantly from that of the incoherent neutron scattering spectra (INSS) calculated from the same MD simulation results. We further examined contributions of the mutual and auto-correlations of the atomic fluctuations to THz-TDS and found that the negative value of the former contribution nearly canceled out the positive value of the latter, resulting in a monotonic increase of the reduced absorption cross section. Because of this cancellation, no distinct broad peak was observed in the absorption lineshape function of THz-TDS, whereas the protein boson peak was observed in INSS. The contribution of water molecules to THz-TDS was extremely large for the hydrated protein at temperatures above 200 K, in which large-amplitude motions of water were excited. The combination of THz-TDS, INSS and MD simulations has the potential to extract function-relevant protein dynamics occurring on the picosecond to nanosecond timescale.
著者
Kazuhiro Takemura Akio Kitao
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.16, pp.295-303, 2019 (Released:2019-11-29)
参考文献数
36

Rigid-body protein-protein docking is very efficient in generating tens of thousands of docked complex models (decoys) in a very short time without considering structure change upon binding, but typical docking scoring functions are not necessarily sufficiently accurate to narrow these decoys down to a small number of plausible candidates. Flexible refinements and sophisticated evaluation of the decoys are thus required to achieve more accurate prediction. Since this process is time-consuming, an efficient screening method to reduce the number of decoys is necessary immediately following rigid-body dockings. We attempted to develop an efficient screening method by clustering decoys generated by the rigid-body docking ZDOCK. We introduced the three metrics ligand-root-mean-square deviation (L-RMSD), interface-ligand-RMSD (iL-RMSD), and the fraction of common contacts (FCC), and examined various ranges of cut-offs for clusters to determine the best set of clustering parameters. Although the employed clustering algorithm is simple, it successfully reduced the number of decoys. Using iL-RMSD with a cut-off radius of 8 Å, the number of decoys that contain at least one near-native model with 90% probability decreased from 4,808 to 320, a 93% reduction in the original number of decoys. Using FCC for the clustering step, the top 1,000 success rates, defined as the probability that the top 1,000 models contain at least one near-native structure, reached 97%. We conclude that the proposed method is very efficient in selecting a small number of decoys that include near-native decoys.
著者
Hiroyuki Terashima Akihiro Kawamoto Yusuke V. Morimoto Katsumi Imada Tohru Minamino
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.14, pp.191-198, 2017 (Released:2017-12-19)
参考文献数
57
被引用文献数
1 17

The bacterial flagellum is a supramolecular motility machine consisting of the basal body as a rotary motor, the hook as a universal joint, and the filament as a helical propeller. Intact structures of the bacterial flagella have been observed for different bacterial species by electron cryotomography and subtomogram averaging. The core structures of the basal body consisting of the C ring, the MS ring, the rod and the protein export apparatus, and their organization are well conserved, but novel and divergent structures have also been visualized to surround the conserved structure of the basal body. This suggests that the flagellar motors have adapted to function in various environments where bacteria live and survive. In this review, we will summarize our current findings on the divergent structures of the bacterial flagellar motor.
著者
Kazuho Yoshida Takahiro Yamashita Kengo Sasaki Keiichi Inoue Yoshinori Shichida Hideki Kandori
出版者
The Biophysical Society of Japan
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.14, pp.183-190, 2017 (Released:2017-12-19)
参考文献数
44
被引用文献数
2

We previously showed that the chimeric proteins of microbial rhodopsins, such as light-driven proton pump bacteriorhodopsin (BR) and Gloeobacter rhodopsin (GR) that contain cytoplasmic loops of bovine rhodopsin, are able to activate Gt protein upon light absorption. These facts suggest similar protein structural changes in both the light-driven proton pump and animal rhodopsin. Here we report two trials to engineer chimeric rhodopsins, one for the inserted loop, and another for the microbial rhodopsin template. For the former, we successfully activated Gs protein by light through the incorporation of the cytoplasmic loop of β2-adrenergic receptor (β2AR). For the latter, we did not observe any G-protein activation for the light-driven sodium pump from Indibacter alkaliphilus (IndiR2) or a light-driven chloride pump halorhodopsin from Natronomonas pharaonis (NpHR), whereas the light-driven proton pump GR showed light-dependent G-protein activation. This fact suggests that a helix opening motion is common to G protein coupled receptor (GPCR) and GR, but not to IndiR2 and NpHR. Light-induced difference FTIR spectroscopy revealed similar structural changes between WT and the third loop chimera for each light-driven pump. A helical structural perturbation, which was largest for GR, was further enhanced in the chimera. We conclude that similar structural dynamics that occur on the cytoplasmic side of GPCR are needed to design chimeric microbial rhodopsins.
著者
Shigeki Mitaku Ryusuke Sawada
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.305-310, 2016 (Released:2016-11-18)
参考文献数
7
被引用文献数
1 3

“Life” is a particular state of matter, and matter is composed of various molecules. The state corresponding to “life” is ultimately determined by the genome sequence, and this sequence determines the conditions necessary for survival of the organism. In order to elucidate one parameter characterizing the state of “life”, we analyzed the amino acid sequences encoded in the total genomes of 557 prokaryotes and 40 eukaryotes using a membrane protein prediction online tool called SOSUI. SOSUI uses only the physical parameters of the encoded amino acid sequences to make its predictions. The ratio of membrane proteins in a genome predicted by the SOSUI online tool was around 23% for all genomes, indicating that this parameter is controlled by some mechanism in cells. In order to identify the property of genome DNA sequences that is the possible cause of the constant ratio of membrane proteins, we analyzed the nucleotide compositions at codon positions and observed the existence of systematic biases distinct from those expected based on random distribution. We hypothesize that the constant ratio of membrane proteins is the result of random mutations restricted by the systematic biases inherent to nucleotide codon composition. A new approach to the biological sciences based on the holistic analysis of whole genomes is discussed in order to elucidate the principles underlying “life” at the biological system level.
著者
Takako Sakano Md. Iqbal Mahamood Takefumi Yamashita Hideaki Fujitani
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.181-194, 2016 (Released:2016-07-14)
参考文献数
39
被引用文献数
13

The accurate prediction of a ligand–protein complex structure is important for computer-assisted drug development. Although many docking methods have been developed over the last three decades, the success of binding structure prediction remains greatly limited. The purpose of this study was to demonstrate the usefulness of molecular dynamics (MD) simulation in assessing a docking pose predicted using a docking program. If the predicted pose is not unstable in an aqueous environment, MD simulation equilibrates the system and removes the ligand from the predicted position. Here we investigated two proteins that are important potential therapeutic targets: β2 adrenergic receptor (β2AR) and PR-Set7. While β2AR is rigid and its ligands are very similar to the template ligand (carazolol), PR-Set7 is very flexible and its ligands vary greatly from the template ligand (histone H4 tail peptide). On an empirical basis, we usually expect that the docking prediction is accurate when the protein is rigid and its ligands are similar to the template ligand. The MD analyses in this study clearly suggested such a tendency. Furthermore, we discuss the possibility that the MD simulation can predict the binding pose of a ligand.
著者
Ichiro Yamato Yoshimi Kakinuma Takeshi Murata
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.37-44, 2016 (Released:2016-02-27)
参考文献数
39
被引用文献数
5

Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases.