Overview of Protein Structure Prediction

 Written by: Fatahiya Mohamed Tap

Based on structural perspective, protein is an ordered structure of the unique linear chain of amino acids.  The tertiary structure of protein is represented by the distribution of secondary structures.  The secondary structure is defined by the presence of hydrogen bond patterns between hydrogen atoms of the amino acid and the oxygen atom of the carboxyl groups in the polypeptide chain.  The functional properties of the protein can be determined from the known tertiary structure of the protein.  Thus, the generation of this tertiary structure is vital in understanding the functional and structural properties of a protein.

Structural bioinformatics is an important area in the field of computational biology.  It focuses on the prediction and analyses of structures which are mainly protein and DNA [1]  Conventionally, the tertiary structure information of protein is obtained through experimental methods such as protein crystallography (X-ray diffraction), and nuclear magnetic resonance (NMR).  The structures obtained from these methods can be further used to investigate the protein folds, evolution, and structure-function relationship.

However, the determination of protein structure through experimental approach is expensive and time-consuming [1].  The difficulty in finding the structure of a protein has generated a large gap between the number of sequences of amino acids and the number of tertiary structures of proteins.  Only a small number of amino acid sequences have their tertiary structures solved using the experimental method.  Thus, this gap motivated the researchers to predict the tertiary structure of proteins using computational approaches [2].  Computational approaches are fast and non-expensive compared to the experimental approaches.  Thus, several computational methods have been developed in order to predict the tertiary structure of proteins.  These methods are:

i           Homology modelling/Comparative modelling

ii          Fold recognition

iii         Ab initio

The threading and comparative modelling methods are the fastest and effective approaches in predicting the structure of protein because these two methods are based on known template structures with the availability of fold library [3], [4].  These methods can predict the tertiary structures of proteins with high accuracy. The models can be applied in the field of drug design, virtual screening and site-directed mutagenesis [5].

References

[1]       M. Dorn, M. B. e Silva, L. S. Buriol, and L. C. Lamb, “Three-dimensional protein structure prediction: Methods and computational strategies,” Comput. Biol. Chem., vol. 53, no. Part B, pp. 251–276, 2014.

[2]       H. Deng, Y. Jia, and Y. Zhang, “Protein structure prediction,” Int. J. Mod. physics. B, vol. 32, no. 18, p. 1840009, Jul. 2018.

[3]       V. K. Vyas, R. D. Ukawala, M. Ghate, and C. Chintha, “Homology Modeling a Fast Tool for Drug Discovery: Current Perspectives,” Indian J. Pharm. Sci., vol. 74, no. 1, pp. 1–17, Jun. 2012.

[4]       S. D. Lam, S. Das, I. Sillitoe, and C. Orengo, “An overview of comparative modelling and resources dedicated to large-scale modelling of genome sequences,” Acta Crystallogr. Sect. D, Struct. Biol., vol. 73, no. Pt 8, pp. 628–640, Aug. 2017.

[5]       T. Schmidt, A. Bergner, and T. Schwede, “Modelling three-dimensional protein structures for applications in drug design,” Drug Discov. Today, vol. 19, no. 7, pp. 890–897, Jul. 2014.