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出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.53, no.6, pp.340, 2013 (Released:2013-11-25)
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
7

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
4

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
和田 卓巳 廣中 謙一 黒田 真也
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.61, no.5, pp.288-292, 2021 (Released:2021-09-28)
参考文献数
16

Organisms can adapt to the environment robustly despite large heterogeneity of cellular response. Heterogeneity of cellular responses has been regarded as noise, which reduces accurate information transmission. The heterogeneity consists of intracellular variation caused by stochasticity of biochemical reactions, and intercellular variation caused by differences in amounts of molecules (cell-to-cell variability). We found that intercellular variation increases gradualness of the multi-cellular dose-response (response diversity effect), resulting in increase of accuracy of information transmission. This “response diversity effect” is a novel mechanism that enables multi-cellular organisms to utilize cell-to-cell variability as information not noise.
著者
伊藤 光二 原口 武士 玉那覇 正典 鈴木 花野 村田 武士
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.63, no.2, pp.91-96, 2023 (Released:2023-05-25)
参考文献数
20

生物界最速ミオシンが淡水産藻類シャジクモに存在することが予見されていたが,その実体は不明であった.最近,私達はそのクローニングに成功し,さらに,最速のミオシンクラスであるミオシン11の高解像度結晶構造解析に世界で初めて成功し,最速ミオシンの秘密はアクチンとの結合領域にあることを明らかにした.
著者
井上 大介
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.62, no.1, pp.24-27, 2022 (Released:2022-03-25)
参考文献数
16

これまで,微小管のダイナミクスは,その末端でのみ生じると考えられてきたが,最近,格子中心部でも発生することが明らかとなってきた.本稿では,微小管格子内ダイナミクスに関する最近の研究について解説し,その中で,筆者らの生体分子モーターによる微小管格子内ダイナミクスの促進に関する研究について紹介する.
著者
永井 健治 松田 知己
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.55, no.6, pp.305-310, 2015 (Released:2015-11-28)
参考文献数
30

After the gene cloning and development of GFP color variants about 20 years ago, fluorescent and luminescent proteins have become indispensable tools for biological research. Their genetically encodablity and light-emitting property has revolutionized our research ability by allowing the visualization of variety of living specimen ranging from biochemical events, proteins, cells, and organisms. Detailed understanding of the physicochemical mechanisms responsible for light generation has helped drive performance improvements and application development. Here we will cover basics of light-emitting proteins, as well as the use of them for bioimaging and biomanipulation.
著者
阿部 一啓
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.59, no.2, pp.073-078, 2019 (Released:2019-03-26)
参考文献数
18

When we have food intake, pH of the stomach reaches around 1. This highly acidic environment is indispensable for the digestion. Gastric proton pump, H+,K+-ATPase is a membrane protein responsible for the gastric acid secretion. Its crystal structures now reveal how this proton pump extrudes H+ even into the pH 1 environment of the stomach.
著者
佐藤 純
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.62, no.6, pp.334-337, 2022 (Released:2023-01-25)
参考文献数
7

複眼の六角形タイル構造は物理的に安定と言われ,細胞形態が物理的制約に従って決められているという考えと合致する.しかし,ある種の変異体においては物理的に不安定な四角形タイルに変化する.ハエの複眼が六角形および四角形タイルを示す機構を解明することにより,細胞形態を幾何学的に制御するメカニズムを明らかにした.
著者
平塚 祐一 新田 高洋
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.62, no.2, pp.137-139, 2022 (Released:2022-05-25)
参考文献数
6

筋肉は分子レベルから階層的に組み上げられた精巧な分子システムである.我々は工学的なアプローチで筋肉の人工合成(人工筋肉)とメカニズムの解明を目指している.本稿では,遺伝子工学的に改変したモータータンパク質を用いて,光照射した特定の部位に人工筋肉を自発的に形成させる手法と,その応用例について解説する.
著者
下林 俊典 大崎 雄樹
出版者
一般社団法人 日本生物物理学会
雑誌
生物物理 (ISSN:05824052)
巻号頁・発行日
vol.60, no.5, pp.267-271, 2020 (Released:2020-09-30)
参考文献数
14

Recently, there is growing evidence in the field of cell biology that membrane-less organelles or condensates are formed by liquid-liquid phase separation (LLPS), as well as some types of membrane-bound organelles like lipid rafts and lipid droplets. Biophysical analyses are powerful and indispensable to elucidate those structures, dynamics and (dys)functions. Here, we combine in vivo intracellular imaging with in vitro synthetic biology and soft-matter physics, to show a new avenue for understanding the biophysics of LLPS-driven organelles. In this review, we particularly discuss macro-to-micro phase separation in lipid rafts and liquid-liquid crystal phase transition in lipid droplets.