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Prediction of Residue Status to Be Protected or Not Protected From Hy-drogen Exchange Using Amino Acid Sequence Only.

Nikita V D, Oxana V G - Open Biochem J (2008)

Bottom Line: Important functional properties are related to flexible segments.Our approach FoldUnfold for the prediction of unstructured regions has been applied to seven different proteins.An additional goal of our study is to assess whether properties inferred using the bioinformatics approach are easily applicable to predict behavior of proteins in solution.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Research, Russian Academy of Sciences, Institutskaya str., 4 Pushchino, Moscow Region, 142290, Russia.

ABSTRACT
We have outlined here some structural aspects of local flexibility. Important functional properties are related to flexible segments. We try to predict regions that have been shown to exhibit the highest probability of being folded in the equilibrium intermediate or native state and will be protected from hydrogen exchange using amino acid sequence only. Our approach FoldUnfold for the prediction of unstructured regions has been applied to seven different proteins. For 80% of the residues considered in this paper we can predict correctly their status: will they be protected or not from hydrogen exchange. An additional goal of our study is to assess whether properties inferred using the bioinformatics approach are easily applicable to predict behavior of proteins in solution.

No MeSH data available.


Comparison of predicted and experimental protection factors for three proteins (a) 2ci2, (b) 2eql, (c) 6pti. Dotted curves are predictions made by our FoldUnfold method with window size of 11 residues. Values that are lower than 20.4 are considered as unprotected and correspond to zero, other values normalized on the average difference between the expected number of contacts and the threshold value of 20.4. Solid curves are original protection factors presented as 0 for unprotected residues and more than 0 for protected residues (normalized on the average protection factor for protected residues). Straight lines represent regular secondary structure according to the DSSP program [26].
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Figure 1: Comparison of predicted and experimental protection factors for three proteins (a) 2ci2, (b) 2eql, (c) 6pti. Dotted curves are predictions made by our FoldUnfold method with window size of 11 residues. Values that are lower than 20.4 are considered as unprotected and correspond to zero, other values normalized on the average difference between the expected number of contacts and the threshold value of 20.4. Solid curves are original protection factors presented as 0 for unprotected residues and more than 0 for protected residues (normalized on the average protection factor for protected residues). Straight lines represent regular secondary structure according to the DSSP program [26].

Mentions: The results of calculations are summarized in Table 3. As shown from the Table, the best scores belong to the size of 11 amino acids. We also tried the sliding window size of 13 amino acids, but this leads to lower results as compared to those of 11 amino acids (data not shown). One can see that for protein alpha-lactalbumin (pdb code 1hml) we have got the maximum accuracy – 97%. A little bit lower results were obtained for other proteins, thus proteins 1hrc, 2eql, 2rn2 and 6pti have about 80% of accuracy (sensitivity) on average (see Fig. 1). The next important question that arises is whether the accuracy (sensitivity) is true in terms of specificity. We have calculated the amount of false positive predictions for every protein (specificity) as well. It can be seen from the table that the results vary greatly, from 35% to 60 %, which is about 40% on average. It should be underlined that the majority of mispredictions for proteins represent cases in which protection was predicted but not observed.


Prediction of Residue Status to Be Protected or Not Protected From Hy-drogen Exchange Using Amino Acid Sequence Only.

Nikita V D, Oxana V G - Open Biochem J (2008)

Comparison of predicted and experimental protection factors for three proteins (a) 2ci2, (b) 2eql, (c) 6pti. Dotted curves are predictions made by our FoldUnfold method with window size of 11 residues. Values that are lower than 20.4 are considered as unprotected and correspond to zero, other values normalized on the average difference between the expected number of contacts and the threshold value of 20.4. Solid curves are original protection factors presented as 0 for unprotected residues and more than 0 for protected residues (normalized on the average protection factor for protected residues). Straight lines represent regular secondary structure according to the DSSP program [26].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570557&req=5

Figure 1: Comparison of predicted and experimental protection factors for three proteins (a) 2ci2, (b) 2eql, (c) 6pti. Dotted curves are predictions made by our FoldUnfold method with window size of 11 residues. Values that are lower than 20.4 are considered as unprotected and correspond to zero, other values normalized on the average difference between the expected number of contacts and the threshold value of 20.4. Solid curves are original protection factors presented as 0 for unprotected residues and more than 0 for protected residues (normalized on the average protection factor for protected residues). Straight lines represent regular secondary structure according to the DSSP program [26].
Mentions: The results of calculations are summarized in Table 3. As shown from the Table, the best scores belong to the size of 11 amino acids. We also tried the sliding window size of 13 amino acids, but this leads to lower results as compared to those of 11 amino acids (data not shown). One can see that for protein alpha-lactalbumin (pdb code 1hml) we have got the maximum accuracy – 97%. A little bit lower results were obtained for other proteins, thus proteins 1hrc, 2eql, 2rn2 and 6pti have about 80% of accuracy (sensitivity) on average (see Fig. 1). The next important question that arises is whether the accuracy (sensitivity) is true in terms of specificity. We have calculated the amount of false positive predictions for every protein (specificity) as well. It can be seen from the table that the results vary greatly, from 35% to 60 %, which is about 40% on average. It should be underlined that the majority of mispredictions for proteins represent cases in which protection was predicted but not observed.

Bottom Line: Important functional properties are related to flexible segments.Our approach FoldUnfold for the prediction of unstructured regions has been applied to seven different proteins.An additional goal of our study is to assess whether properties inferred using the bioinformatics approach are easily applicable to predict behavior of proteins in solution.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Research, Russian Academy of Sciences, Institutskaya str., 4 Pushchino, Moscow Region, 142290, Russia.

ABSTRACT
We have outlined here some structural aspects of local flexibility. Important functional properties are related to flexible segments. We try to predict regions that have been shown to exhibit the highest probability of being folded in the equilibrium intermediate or native state and will be protected from hydrogen exchange using amino acid sequence only. Our approach FoldUnfold for the prediction of unstructured regions has been applied to seven different proteins. For 80% of the residues considered in this paper we can predict correctly their status: will they be protected or not from hydrogen exchange. An additional goal of our study is to assess whether properties inferred using the bioinformatics approach are easily applicable to predict behavior of proteins in solution.

No MeSH data available.