Comparative Molecular Dynamics of Mesophilic and Psychrophilic Protein Homologues Studied by 1.2 ns Simulations

Abstract

It is well established that the dynamic motion of proteins plays an important functional role, and that the adaptation of a protein molecule to its environment requires optimization of internal non-covalent interactions and protein-solvent interactions. Serine proteinases in general, and trypsin in particular has been used as a model system in exploring possible structural features for cold adaptation. In this study, a 500 p.s. and a 1200 p.s. molecular dynamics (MD) simulation at 300 K of both anionic salmon trypsin and cationic bovine trypsin are analyzed in terms of molecular flexibility, internal non-covalent interactions and protein-solvent interactions. The present MD simulations do not indicate any increased flexibility of the cold adapted enzyme on an overall basis. However, the apparent higher flexibility and deformability of the active site of anionic salmon trypsin may lower the activation energy for ligand binding and for catalysis, and might be a reason for the increased binding affinity and catalytic efficiency compared to cationic bovine trypsin.

Comparative structural studies of psychrophilic and mesophilic protein homologues by molecular dynamics simulation

“…Analogous finding has been reported from comparative molecular dynamics studies of psychrophilic and mesophilic uracil DNA glycosylase (UDG) where investigators have shown that at 300 K enhanced flexibility lies locally in the loop region involved in DNA recognition [29]. Comparative molecular dynamics studies of psychrophilic and mesophilic trypsin reported that the active site of psychrophilic trypsin shows an apparent higher flexibility and deformability at 300 K [10]. Recently it has been reported that at 300 K psychrophilic trypsin and elastase show enhanced localized flexibility in the loop regions, which confers larger flexibility to these enzymes [7].…”

“…At 373 K pMa loses all 3 10 helices (intermediate, C-and N-terminal) within 1 ns, original b-sheets denature at around 4 ns and rearranged bsheets appears in the structure, a-helix is however stably maintained throughout the simulation. Since intermediate 3 10 helix is absent in Fig. 7.…”

“…Molecular dynamics (MD) simulation is a suitable tool to evaluate the comparative basis of protein thermostability between homologous psychrophilic and mesophilic proteins. However only a few comparative molecular dynamics studies aimed at evaluating temperature dependencies of the dynamics of psychrophilic and mesophilic proteins at different temperatures have been done [6][7][8][9][10]. In fact to our knowledge no comparative molecular dynamics study dealing with wide range of temperature has been reported.…”

“…has an intermediate 3 10 helix (residues 34-36). The rest of the structures comprise mostly of b-bridges and loops.…”

Comparative thermal unfolding study of psychrophilic and mesophilic subtilisin-like serine proteases by molecular dynamics simulations

“…The reduced intramolecular contacts/interactions could destabilize the protein structure (Jaenicke, 1991(Jaenicke, , 2000Pace et al, 1996) while the increased protein-solvent hydrogen-bonding interactions would likely enhance the flexibility of the protein structure (Bandyopadhyay, Chakraborty, & Bagchi, 2005;Brandsdal, Heimstad, Sylte, & Smalås, 1999;Soares, Teixeira, & Baptista, 2003;Tarek & Tobias, 2002). VPR has significantly larger polar SASA but smaller nonpolar SASA than PRK (with the exception of 573 K), thus explaining why VPR has a higher number of proteinsolvent HBs than PRK.…”