In silico designing of therapeutic protein enriched with branched-chain amino acids for the dietary treatment of chronic liver disease.

Sunil, L. and Prasanna, Vasu (2017) In silico designing of therapeutic protein enriched with branched-chain amino acids for the dietary treatment of chronic liver disease. Journal of Molecular Graphics and Modelling, 76. pp. 192-204.

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Abstract

Leucine, isoleucine, and valine are three essential branched-chain amino acids (BCAA) account for 40-45% of total essential amino acids. BCAA stimulates protein synthesis primarily in skeletal muscles, and it can directly transport to circulatory blood stream bypassing the liver. Hence, a protein enriched with BCAA is an important therapeutic target for the dietary treatment of chronic liver disease. The present study is to design a synthetic protein enriched with BCAA and the challenge is to maximize the BCAA content, keeping the balanced ratio of leucine, isoleucine, valine - 2: 1: 1.2 as specified by WHO/UNU/FAO. Here, we turned the general concept of homology modeling and tried to find a suitable scaffold (α-helix) to host an excess amount of BCAA for increased stability and digestibility. A total of 50 protein models were constructed by using SWISS-MODEL, Modeller 9.17, ProtParam tool, and allergen online tools. Out of 50 different protein models, protein model-50 was found to be best, which had a well-defined 3D structure, good in silico digestibility, balanced ratio of BCAA and showed 65.57% structure identity to the template apo-bovine α-lactalbumin (1F6R). Templates search was performed against PDB using PSI-BLAST, SWISS-MODEL, PROFUNC, I-TASSER, and ConSurf. The secondary structure was predicted by PSSPred, PSIPRED, I-TASSER, PORTER, and SPIDER2. The modeled structure of protein Model-50 was validated by PROCHECK, ERRAT, ProSA, and QMEAN. COACH and ProFUNC tools were performed to determine the functional effects of protein model-50. Overall, the BCAA was enriched from 22 to 56.4% with the balanced ratio of Leu: Ile: Val (2: 1: 1.2). The Ramachandran plot showed 97.7% of the amino acid residues in allowed regions with ERRAT score of 86.05. We have successfully modeled the complete three-dimensional structure of the target protein model-50 using highly reputed computational tools.

Item Type:	Article
Uncontrolled Keywords:	3D structure prediction; Apo-bovine α-lactalbumin; Branched-chain amino acids (BCAA); Homology modeling; Protein validation; Secondary structure prediction
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 03 Amino Acid Chemistry
Divisions:	Food Safety Analytical Quality Control Lab
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	14 Feb 2018 03:52
Last Modified:	14 Feb 2018 03:52
URI:	http://ir.cftri.res.in/id/eprint/13402

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