Biomedical subjects

Chi-Hung Tsai

Publications and source records attributed to Chi-Hung Tsai.

4 recordsLinked to original sources

PubMed2006

Disulfide connectivity prediction with 70% accuracy using two-level models.

Disulfide bridges stabilize protein structures covalently and play an important role in protein folding. Predicting disulfide connectivity precisely helps towards the solution of protein structure prediction. Previous methods for disulfide connectivity prediction either infer the bonding potential of cysteine pairs or rank alternative disulfide bonding patterns. As a result, these methods encode data according to cysteine pairs (pair-wise) or disulfide bonding patterns (pattern-wise). However, using either encoding scheme alone cannot fully utilize the local and global information of proteins, so the accuracies of previous methods are limited. In this work, we propose a novel two-level framework to predict disulfide connectivity. With this framework, both the pair-wise and pattern-wise encoding schemes are considered. Our models were validated on the datasets derived from SWISS-PROT 39 and 43, and the results demonstrate that our models can combine both local and global information. Compared to previous methods, significant improvements were obtained by our models. Our work may also provide insights to further improvements of disulfide connectivity prediction and increase its applicability in protein structure analysis and prediction.

Amino Acid Sequence↗

PubMed2005

Improving disulfide connectivity prediction with sequential distance between oxidized cysteines.

SUMMARY: Predicting disulfide connectivity precisely helps towards the solution of protein structure prediction. In this study, a descriptor derived from the sequential distance between oxidized cysteines (denoted as DOC) is proposed. An approach using support vector machine (SVM) method based on weighted graph matching was further developed to predict the disulfide connectivity pattern in proteins. When DOC was applied, prediction accuracy of 63% for our SVM models could be achieved, which is significantly higher than those obtained from previous approaches. The results show that using the non-local descriptor DOC coupled with local sequence profiles significantly improves the prediction accuracy. These improvements demonstrate that DOC, with a proper scaling scheme, is an effective feature for the prediction of disulfide connectivity. The method developed in this work is available at the web server PreCys (prediction of cys-cys linkages of proteins).

Chymotrypsinogen↗

PubMed2004

Cysteine separations profiles on protein sequences infer disulfide connectivity.

MOTIVATION: Disulfide bonds play an important role in protein folding. A precise prediction of disulfide connectivity can strongly reduce the conformational search space and increase the accuracy in protein structure prediction. Conventional disulfide connectivity predictions use sequence information, and prediction accuracy is limited. Here, by using an alternative scheme with global information for disulfide connectivity prediction, higher performance is obtained with respect to other approaches. RESULT: Cysteine separation profiles have been used to predict the disulfide connectivity of proteins. The separations among oxidized cysteine residues on a protein sequence have been encoded into vectors named cysteine separation profiles (CSPs). Through comparisons of their CSPs, the disulfide connectivity of a test protein is inferred from a non-redundant template set. For non-redundant proteins in SwissProt 39 (SP39) sharing less than 30% sequence identity, the prediction accuracy of a fourfold cross-validation is 49%. The prediction accuracy of disulfide connectivity for proteins in SwissProt 43 (SP43) is even higher (53%). The relationship between the similarity of CSPs and the prediction accuracy is also discussed. The method proposed in this work is relatively simple and can generate higher accuracies compared to conventional methods. It may be also combined with other algorithms for further improvements in protein structure prediction. AVAILABILITY: The program and datasets are available from the authors upon request. CONTACT: cykao@csie.ntu.edu.tw.

Algorithms↗

PubMed2002

GEM: a Gaussian Evolutionary Method for predicting protein side-chain conformations.

We have developed an evolutionary approach to predicting protein side-chain conformations. This approach, referred to as the Gaussian Evolutionary Method (GEM), combines both discrete and continuous global search mechanisms. The former helps speed up convergence by reducing the size of rotamer space, whereas the latter, integrating decreasing-based Gaussian mutations and self-adaptive Gaussian mutations, continuously adapts dihedrals to optimal conformations. We tested our approach on 38 proteins ranging in size from 46 to 325 residues and showed that the results were comparable to those using other methods. The average accuracies of our predictions were 80% for chi(1), 66% for chi(1 + 2), and 1.36 A for the root mean square deviation of side-chain positions. We found that if our scoring function was perfect, the prediction accuracy was also essentially perfect. However, perfect prediction could not be achieved if only a discrete search mechanism was applied. These results suggest that GEM is robust and can be used to examine the factors limiting the accuracy of protein side-chain prediction methods. Furthermore, it can be used to systematically evaluate and thus improve scoring functions.

Algorithms↗