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A molecular dynamics approach to explore the structural characterization of cataract causing mutation R58H on human γD crystallin

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Abstract

The crystallins are a family of monomeric proteins present in the mammalian lens and mutations in these proteins cause various forms of cataracts. The aim of our current study is to emphasize the structural characterization of aggregation propensity of mutation R58H on γD crystallin using molecular dynamics (MD) approach. MD result revealed that difference in the sequence level display a wide variation in the backbone atomic position, and thus exhibits rigid conformational dynamics. Changes in the flexibility of residues favoured to increase the number of intra-molecular hydrogen bonds in mutant R58H. Moreover, notable changes in the hydrogen bonding interaction resulted to cause the misfolding of mutant R58H by introducing α-helix. Principal component analysis (PCA) result suggested that mutant R58H showed unusual conformational dynamics along the two principal components when compared to the wild-type (WT)-γD crystallin. In a nutshell, the increased surface hydrophobicity could be the cause of self-aggregation of mutant R58H leading to aculeiform cataract.

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Abbreviations

RMSD:

Root-mean-square deviation

RMSF:

Root-mean-square fluctuation

ASA:

Accessible surface area

DSSP:

Dictionary of secondary structure of protein

PCA:

Principal component analysis

FEL:

Free energy landscape

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Authors and Affiliations

  1. Unit of Biochemistry, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah, Malaysia

    Rohini Karunakaran

  2. Unit of Psychiatry, Faculty of Medicine, AIMST University, Bedong, Malaysia

    P. S. Srikumar

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  1. Rohini Karunakaran
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  2. P. S. Srikumar
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Correspondence to Rohini Karunakaran.

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Karunakaran, R., Srikumar, P.S. A molecular dynamics approach to explore the structural characterization of cataract causing mutation R58H on human γD crystallin. Mol Cell Biochem 449, 55–62 (2018). https://doi.org/10.1007/s11010-018-3342-8

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  • DOI: https://doi.org/10.1007/s11010-018-3342-8

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