Paper presentation Paper presentation

Submitted to: Submitted by:Dr. Durg Vijay Singh Shweta Kumari(Dept. of Biological Science) Roll no: 21

M.Sc Bioinformatics2 nd semesterSession: 2014-16

Introduction

Paper on :

“ “Prediction of the Amount of Secondary Structure in a Prediction of the Amount of Secondary Structure in a Globular Protein from Its Aminoacid Composition Globular Protein from Its Aminoacid Composition (helix/sheet/turns)”(helix/sheet/turns)”

Authors:

W. R. KRIGBAUM AND SARA PARKEY KNLTTTONW. R. KRIGBAUM AND SARA PARKEY KNLTTTON

Published in:

Proc. Nat. Acad. Sci. USA

Vol. 70, No. 10, pp. 2809-2813, October 1973

IntroductionIntroduction Amino acids are biologically important organic compounds composed of

amine (-NH2) and carboxylic acid (-COOH) functional groups, along with a side-chain specific to each amino acid. The amino acids are linked by dehydration synthesis to form peptide bonds to form protein.

The term secondary structure refers to the interaction of the hydrogen bond donor and acceptor residues of the repeating peptide unit. The two most important secondary structures of proteins, the alpha helix and the beta sheet, were predicted by the American chemist Linus Pauling in the early 1950s.

Globular proteins, also known as spheroproteins, are proteins formed by compacted amino acid chains, which are folded into intricate shapes that often roughly resemble spheres.

Importance of prediction of amount of secondary structure in globular protein is, additional protein structure (on the basis of stronger correlation).

Motivation and BackgroundMotivation and Background

Protein crystallographers often undertake the crystal-structure study of a protein when its aminoacid composition, but not the residue sequence, is known.

So, a method for predicting the amounts of the various features of secondary structure (helix, sheet, etc.) from the aminoacid composition could be of considerable use.

Other important application of this, knowledge of the sequence is used to predict the regions of secondary structure.

Method

Base of study: data of 18 proteins of known sequence and structure.

Independent prediction of the A and B subunit of hemoglobin and insulin (total no. Become 20).

Four type of secondary structure are considered: helix (both alpha and 310 helix), beta-sheet, turn and coil.

Data baseData base

Data base cont...

Two types of error found in these data base: Uncertainties in primary structure: chemical and

crystallographic identification of a particular residue differ(Asp and Glu are not differentiated from Asn Gln).

Assignment of the region involves some measure of uncertainty: comparision of helical region of 8 common protein,total residue- 1586, helical residue 570 differenence in 94, the uncertainty is 6% in helical content.

Method for predictionMethod for prediction

To find a positive correlation between the helical content and a parameter obtained by summing the product of the percent composition of each amino acid and the helical potential of the corresponding residue.

Correlations between the sum of the percentage compositions of from one to five selected types of amino acid and the percentages of the various features of secondary structure.

For helical content, 16 combinations yielded a Pearson correlation coefficient, r, of +0.80 or larger, and 8 gave negative coefficients exceeding 0.70 in absolute magnitude (Irl ranges from 0.3 to 0.4 for random).

To sum of up to five amino acids (one giving a positive correlation and the other negative) were combined by a multiple regression technique.

Comparison of the predictions based upon different combinations of amino acids showed that the best pair did not always involve the two sums having the largest Irl values.

Optical rotatory dispersion measurements indicate that apomyoglobin has 20% less helix than myoglobin, which suggests addition of 20% to the calculated helical percentages for oxygen-carrying heme proteins.

ResultResult

The combinations of aminoacid compositions found to give the best predictions are:

here, C - represents the sum of the percentage compositions of His, Asp, and Asn in the protein of interest.

The percentages of the four types of secondary structure are then calculated from the relations:

Note: coefficients were determined from the full data set of 18 proteins.

Heme = 20.00 (for oxygen carrying heme protein otherwise zero)

0

Testing of validity of this procedure was done by the redetermined the coefficients by omitting one protein at a time and used to predict the percentage of helix, sheet and ciol region in 18 protein.

Result was predicting a graph between predicted and assigned percentage.

Line drawn with 45 degree slpoe, perfect alignment.

The amount of secondary structure has been estimated experimentally by:

Circular dichorism

Optical rotatory dispersion

Infrared spectra

Second set of preidictive function was obtained by repetation of this procedure.

The second set combination is:

Second set of relations should furnish an estimate of sufficient reliability for many purpose.

Capable of further refinements to yield more reliable prediction.

Several amino acid combination gave high corelations (both positive and negative) for the four type of secondary structure.

Stronger correlation can predict the protein structure.

Related Work

Conclusion

Multiple regression is used to obtain relationships for predicting the amount of secondary structure in a protein molecule from a knowledge of its amino acid composition.

These relation was tested by using 18 proteins of known structure, but omitting the protein to be predicted.

Independent predictions were made for the two sub-chains of hemoglobin and insulin.

The average errors forthese 20 chains or subchains are: helix ± 7.1%, sheet± 6.9%, turn ± 4.2%, and coil ± 5.7%.

A second set of relations yielding somewhat inferior predictions is given for the case in which Asp and Asn, and Glu and Gln, are not differentiated.

Predictions are also listed for 15 proteins for which the aminoacid sequence or tertiary structure is unknown.

References

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC427114/

http://www.cliffsnotes.com/sciences/biology/biochemistry-i/protein-structure/secondary-structure