Browsing by Author "Liu, Jen-Wei"

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Local Packing Density Is the Main Structural Determinant of the Rate of Protein Sequence Evolution at Site Level
(2014)
Yeh, So-Wei
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Huang, Tsun-Tsao
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Liu, Jen-Wei
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Yu, Sung-Huan
;
Shih, Chien-Hua
Functional and biophysical constraints result in site-dependent patterns of protein sequence variability. It is commonly assumed that the key structural determinant of site-specific rates of evolution is the Relative Solvent Accessibility (RSA). However, a recent study found that amino acid substitution rates correlate better with two Local Packing Density (LPD) measures, the Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This work aims at a more thorough assessment. To this end, in addition to substitution rates, we considered four other sequence variability scores, four measures of solvent accessibility (SA), and other CN measures. We compared all properties for each protein of a structurally and functionally diverse representative dataset of monomeric enzymes. We show that the best sequence variability measures take into account phylogenetic tree topology. More importantly, we show that both LPD measures (WCN and CN) correlate better than all of the SA measures, regardless of the sequence variability score used. Moreover, the independent contribution of the best LPD measure is approximately four times larger than that of the best SA measure. This study strongly supports the conclusion that a site\'s packing density rather than its solvent accessibility is the main structural determinant of its rate of evolution.
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.
Relationships between residue Voronoi volume and sequence conservation in proteins
(2018-02-01)
Liu, Jen-Wei
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Cheng, Chih-Wen
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Lin, Yu-Feng
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Chen, Shao-Yu
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Hwang, Jenn-Kang
Background: Functional and biophysical constraints can cause different levels of sequence conservation in proteins. Previously, structural properties, e.g., relative solvent accessibility (RSA) and packing density of the weighted contact number (WCN), have been found to be related to protein sequence conservation (CS). The Voronoi volume has recently been recognized as a new structural property of the local protein structural environment reflecting CS. However, for surface residues, it is sensitive to water molecules surrounding the protein structure. Herein, we present a simple structural determinant termed the relative space of Voronoi volume (RSV); it uses the Voronoi volume and the van der Waals volume of particular residues to quantify the local structural environment. Methods: RSV (range, 0-1) is defined as (Voronoi volume - van der Waals volume)/Voronoi volume of the target residue. The concept of RSV describes the extent of available space for every protein residue. Results: RSV and Voronoi profiles with and without water molecules (RSVw, RSV, VOw, and VO) were compared for 554 non-homologous proteins. RSV (without water) showed better Pearson's correlations with CS than did RSVw, VO, or VOw values. The mean correlation coefficient between RSV and CS was 0.51, which is comparable to the correlation between RSA and CS (0.49) and that between WCN and CS (0.56). Conclusions: RSV is a robust structural descriptor with and without water molecules and can quantitatively reflect evolutionary information in a single protein structure. Therefore, it may represent a practical structural determinant to study protein sequence, structure, and function relationships.
Site-Specific Structural Constraints on Protein Sequence Evolutionary Divergence: Local Packing Density versus Solvent Exposure
(2014-01-01)
Yeh, So-Wei
;
Liu, Jen-Wei
;
Yu, Sung-Huan
;
Shih, Chien-Hua
;
Hwang, Jenn-Kang
Protein sequences evolve under selection pressures imposed by functional and biophysical requirements, resulting in site-dependent rates of amino acid substitution. Relative solvent accessibility (RSA) and local packing density (LPD) have emerged as the best candidates to quantify structural constraint. Recent research assumes that RSA is the main determinant of sequence divergence. However, it is not yet clear which is the best predictor of substitution rates. To address this issue, we compared RSA and LPD with site-specific rates of evolution for a diverse data set of enzymes. In contrast with recent studies, we found that LPD measures correlate better than RSA with evolutionary rate. Moreover, the independent contribution of RSA is minor. Taking into account that LPD is related to backbone flexibility, we put forward the possibility that the rate of evolution of a site is determined by the ease with which the backbone deforms to accommodate mutations.