Thermo-Effects Of Methionine Aminopeptidase: Molecular Dynamics Studies

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Date
2006-07
Authors
Chin, Sek Peng
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Abstract
To date, numerous factors have been considered for putative determinants of protein thermostability. Yet, there is no universal theory or rule to explain the principles underlying protein thermostability, as thermostability appears to be interplayed by many factors. In this current work, molecular dynamics simulations were used to investigate thermal adaptation differences between methionine aminopeptidase from hyperthermophile, Pyrococcus furiosus (PfMAP) , and mesophile, Escherichia coli (EcMAP). EcMAP and PfMAP were simulated at 300 K, 373 K and 500 K. It was found that PfMAP possessed higher number of salt bridges and ionic network, together with an increased number of strong and medium hydrogen bonds. Salt bridges played an important role in stabilizing loop-helix and helices regions, C-terminal and also retaining the integrity of its active site. Salt bridges and ionic networks are believed to strengthen the stability of PfMAP by linking sequentially distant segments which contribute into the stabilization of the tertiary structure of PfMAP. Strong hydrogen bonds in PfMAP at 373 K were mostly placed at the junction between large and small domains, which is important to hold these two domains together and to stabilize the small domain. The results revealed that PfMAP is not only stable but has relatively higher flexibility at both 300 and 373 K as compared to EcMAP. Structural flexibility of PfMAP is believed to contribute towards the conformational entropy changes during unfolding hence increased the free energy of stabilization at high temperature. Solvent accessible surface area and root mean square deviations analysis also proved that PfMAP active site conformation is well without being affected by overall flexibility and solvent penetration.
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Putative determinants of , protein thermostability.
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