Rationalization of poor solubility of TGF-β3 using MD simulation.
Despite sequence and structural similarity, TGF-β3 has low solubility among other isoforms of TGF-β. We used nanosecond of molecular dynamic simulations (MD) with explicit solvent, alone and in presence of urea, to investigate the intermediates resulting from the unfolding process of TGF-β3 and TGF-β1. MD simulations of the full-length proteins show a very early loss of α-helix in TGF-β3 compared to the one in the TGF-β1. MD simulation of a small fragment consisting of H3 α-helix of TGF-β3 shows conversion of this segment to β-sheet. Relative instability of H3 α-helix in TGF-β3 and its propensity to form β-sheet may explain the poor solubility of TGF-β3 compared to TGF-β1. The other reasons for poor solubility of TGF-β3 may be the hydrophobic patches on its surface and low charge over the entire range of pH.
Nayeem
Shahid M
SM
Department of Chemistry, Indian Institute of Technology, Delhi, India.
Deep
Shashank
S
D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012995:Solubility; D012997:Solvents; D053773:Transforming Growth Factor beta1 / Q000737:chemistry; D053782:Transforming Growth Factor beta3 / Q000737:chemistry*
D010446:Peptide Fragments; D012997:Solvents; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3