Browsing by Author "Lin, Jau-Ji"

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On the packing density of the unbound protein-protein interaction interface and its implications in dynamics
(2015-01-21)
Lin, Jau-Ji
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Lin, Zih-Lin
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Hwang, Jenn-Kang
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Huang, Tsun-Tsao
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生物資訊及系統生物研究所
Background: Characterizing the interface residues will help shed light on protein-protein interactions, which are involved in many important biological processes. Many studies focus on characterizing sequence or structure features of protein interfaces, but there are few studies characterizing the dynamics of interfaces. Therefore, we would like to know whether there is any specific dynamics pattern in the protein-protein interaction interfaces. Thermal fluctuation is an important dynamical property for a residue, and could be quickly estimated by local packing density without large computation since studies have showen closely relationship between these two properties. Therefore, we divided surface of an unbound subunit (free protein subunits before they are involved in forming the protein complexes) into several separate regions, and compared their average thermal fluctuations of different regions in order to characterize the dynamics pattern in unbound protein-protein interaction interfaces. Results: We used weighted contact numbers (WCN), a parameter-free method to quantify packing density, to estimate the thermal fluctuations of residues in the interfaces. By analyzing the WCN distributions of interfaces in unbound subunits from 1394 non-homologous protein complexes, we show that the residues in the central regions of interfaces have higher packing density (i.e. more rigid); on the other hand, residues surrounding the central regions have smaller packing density (i.e. more flexible). The distinct distributions of packing density, suggesting distinct thermal fluctuation, reveals specific dynamics pattern in the interface of unbound protein subunits. Conclusions: We found general trend that the unbound protein-protein interaction interfaces consist of rigid residues in the central regions, which are surrounded by flexible residues. This finding suggests that the dynamics might be one of the important features for the formation of protein complexes.
On the relationship between residue structural environment and sequence conservation in proteins
(2017-09-01)
Liu, Jen-Wei
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Lin, Jau-Ji
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Cheng, Chih-Wen
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Lin, Yu-Feng
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Hwang, Jenn-Kang
Residues that are crucial to protein function or structure are usually evolutionarily conserved. To identify the important residues in protein, sequence conservation is estimated, and current methods rely upon the unbiased collection of homologous sequences. Surprisingly, our previous studies have shown that the sequence conservation is closely correlated with the weighted contact number (WCN), a measure of packing density for residue's structural environment, calculated only based on the C-alpha positions of a protein structure. Moreover, studies have shown that sequence conservation is correlated with environment-related structural properties calculated based on different protein substructures, such as a protein's all atoms, backbone atoms, side-chain atoms, or side-chain centroid. To know whether the C-alpha atomic positions are adequate to show the relationship between residue environment and sequence conservation or not, here we compared C-alpha atoms with other substructures in their contributions to the sequence conservation. Our results show that C-alpha positions are substantially equivalent to the other substructures in calculations of various measures of residue environment. As a result, the overlapping contributions between C-alpha atoms and the other substructures are high. yielding similar structure-conservation relationship. Take the WCN as an example, the average overlapping contribution to sequence conservation is 87% between C-alpha, and all-atom substructures. These results indicate that only C-alpha atoms of a protein structure could reflect sequence conservation at the residue level.
Prediction of Metal Ion-Binding Sites in Proteins Using the Fragment Transformation Method
(2012-06-18)
Lu, Chih-Hao
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Lin, Yu-Feng
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Lin, Jau-Ji
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Yu, Chin-Sheng
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生物資訊及系統生物研究所
The structure of a protein determines its function and its interactions with other factors. Regions of proteins that interact with ligands, substrates, and/or other proteins, tend to be conserved both in sequence and structure, and the residues involved are usually in close spatial proximity. More than 70,000 protein structures are currently found in the Protein Data Bank, and approximately one-third contain metal ions essential for function. Identifying and characterizing metal ion-binding sites experimentally is time-consuming and costly. Many computational methods have been developed to identify metal ion-binding sites, and most use only sequence information. For the work reported herein, we developed a method that uses sequence and structural information to predict the residues in metal ion-binding sites. Six types of metal ion-binding templates-those involving Ca2+, Cu2+, Fe3+, Mg2+, Mn2+, and Zn2+-were constructed using the residues within 3.5 angstrom of the center of the metal ion. Using the fragment transformation method, we then compared known metal ion-binding sites with the templates to assess the accuracy of our method. Our method achieved an overall 94.6 % accuracy with a true positive rate of 60.5 % at a 5 % false positive rate and therefore constitutes a significant improvement in metal-binding site prediction.