In Silico Biology - Volume 6, issue 1-2

Authors: Kaur, Harpreet | Raghava, Gajendra Pal Singh

Article Type: Research Article

Abstract: In this study, an attempt has been made to develop a method for predicting weak hydrogen bonding interactions, namely, C^{α} -H·O and C^{α} -H·π interactions in proteins using artificial neural network. Both standard feed-forward neural network (FNN) and recurrent neural networks (RNN) have been trained and tested using five-fold cross-validation on a non-homologous dataset of 2298 protein chains where no pair of sequences has more than 25% sequence identity. It …has been found that the prediction accuracy varies with the separation distance between donor and acceptor residues. The maximum sensitivity achieved with RNN for C^{α} -H·O is 51.2% when donor and acceptor residues are four residues apart (i.e. at Δ_{D-A} =4) and for C^{α} -H·π is 82.1% at Δ_{D-A} =3. The performance of RNN is increased by 1–3% for both types of interactions when PSIPRED predicted protein secondary structure is used. Overall, RNN performs better than feed-forward networks at all separation distances between donor-acceptor pair for both types of interactions. Based on the observations, a web server CHpredict (available at http://www.imtech.res.in/raghava/chpredict/) has been developed for predicting donor and acceptor residues in C^{α} -H·O and C^{α} -H·π interactions in proteins. Show more

Keywords: Weak hydrogen bonds, donor, acceptor, prediction, neural network, secondary structure

Citation: In Silico Biology, vol. 6, no. 1-2, pp. 111-125, 2006

Authors: Seshasayee, Aswin Sai Narain

Article Type: Research Article

Abstract: Protein-protein interaction networks are useful in contextual annotation of protein function and in general to achieve a system-level understanding of cellular behavior. This work reports on the social behavior of the yeast protein-protein interaction network and concludes that it is non-random. This work, while providing an analysis of organization of genes into functional societies, can potentially be useful in assessing the accuracy of contextual gene annotation based on such interaction networks.

Keywords: Protein-protein interaction, small world, clustering coefficient, pathway, contextual annotation

Citation: In Silico Biology, vol. 6, no. 1-2, pp. 127-130, 2006

Authors: Bock, Christoph | Hesser, Jürgen

Article Type: Research Article

Abstract: High sequence identity between two proteins (e.g. > 60% is a strong evidence for high structural similarity. However, internal shifts in one of the two proteins can sometimes give rise to unexpectedly high structural differences. This, in turn, causes unreliable structure predictions when two such proteins are used in homology modeling. Here, we perform a computational analysis of helix shifts and we show that their occurrence can be predicted with statistical learning methods. Our …results indicate that helix shifts increase the RMS error by factor 2.6 compared to those protein pairs without a helix shift. Although helix shifts are rare (1.6% of helices and a commensurately higher number of proteins are affected), they therefore pose a significant problem for reliable structure prediction systems. In this paper, we prototype a new approach for model quality assessment and demonstrate that it can successfully warn against helix shifts. A support vector machine trained on a wide range of sequence and structure properties predicts the occurrence of helix shifts with a sensitivity of 74.2% and a specificity of 83.6%. On an equalized test dataset, this corresponds to an accuracy of 78.9%. Projected to the full dataset, it translates to an accuracy of 83.4%. Our analysis shows that helix shift detection is a valuable building block for highly reliable structure prediction systems. Furthermore, the statistical learning based approach to helix shift detection that we employ here is orthogonal to well-established model quality assessment methods (which use geometric constraint checking or mean force potentials). Therefore, a further increase of prediction accuracy is expected from the combination of these methods. Show more

Keywords: Comparative modeling, homology modeling, error sources, MQAP, helix movement, secondary structure

Citation: In Silico Biology, vol. 6, no. 1-2, pp. 131-145, 2006

Authors: Mizuta, Satoshi | Munakata, Hikaru | Aimaiti, Abulimiti | Oya, Ichitaro | Oosawa, Kenji | Shimizu, Toshio

Article Type: Research Article

Abstract: Genomes contain various types of repetitive sequences. They may be used as probes for seeking genome rearrangements because they are rather free from the natural selection if they are located in the intergenic regions. In this study, we searched for tandem repeats (TRs) in 44 prokaryotic genomes by the color-coding method and sought the signs of genome rearrangements by detailed analysis of the detected TRs. We found 13,542 tandem repeats from 44 prokaryotic genomes in total …ranging from several tens to one thousand per genome. The results of statistical analysis show that TRs tend to exist on high base composition bias regions in some genomes. Moreover, we recognized the characteristic distribution patterns of equivalent TR-pairs in 12 genomes, which are expected to indicate the occurrence of whole-genome duplication (WGD) on the genomes. It is demonstrated that TRs could indeed be used for seeking genome rearrangements. Although it has not been made clear at this time whether or not WGD had occurred in prokaryotic genomes, the results of the analyses of equivalent TR-pairs in this study are thought to be evidences of WGD in these genomes. Show more

Keywords: Tandem repeats, color-coding, genome rearrangement, prokaryotes

Citation: In Silico Biology, vol. 6, no. 1-2, pp. 147-159, 2006