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

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Relation http://ir.cftri.com/13402/
http://dx.doi.org/doi:10.1016/j.jmgm.2017.06.015
 
Title In silico designing of therapeutic protein enriched with
branched-chain amino acids for the dietary treatment of
chronic liver disease.
 
Creator Sunil, L.
Prasanna, Vasu
 
Subject 03 Amino Acid Chemistry
 
Description 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.
 
Date 2017
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13402/1/Journal%20of%20Molecular%20Graphics%20and%20Modelling%202017.pdf
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.