Myoglobin structure, molecular dynamics

Most potential energy surfaces are extremely complex. Fiber and Karplus analyzed a 300 psec molecular dynamics trajectory of the protein myoglobin. They estimate that 2000 thermally accessible minima exist near the native protein structure. The total number of conformations is even larger. Dill derived a formula to calculate the upper bound of thermally accessible conformations in a protein. Using this formula, a protein of 150 residues (the approx-... 

Figure 61. Positional error in refinement of the 25-ps data from myoglobin simulation The deviations between atomic positions are calculated after the molecular dynamics average structure and the refined structures are superimposed by least squares. The deviations for backbone atoms (N, C, and C", solid line) and sidechain atoms (dotted line) are averaged over residues.

Lormnas, V. and Pettitt, B.M. (1994) A connected cluster of hydration around myoglobin correlation between molecular-dynamics simulations and experiment. Proteins Structure, Function, and Genetics, 18, 133-147. 

In contrast to Me cyts bs, the thermodynamic equilibrium ratio of A B isomers of 1 1.3 in OM cyt bs favors isomer B, and is obtained only after hours at 65 °C. At physiological temperature, the OM cyt bs heme is kinetically trapped. Several other properties of rat OM cyt bs differ from those of rat Me cyt bs. - (i) OM cyt bs has a significantly lower redox potential than Me cyt bs (Table 2) (ii) OM cyt bs T, 83.6 °C) is more stable toward thermal denaturation than Me cyt bs (7m, 65.2 °C). (iii) OM cyt bs is about lOkJmol ( 2.5kcalmol ) more stable than Me cyt bs towards chemical denaturation (iv) while bovine Me cyt bs will release heme to apo-myo obin at pH 7.0, heme is not transferred from rat OM cyt bs to apo-myoglobin even at pH values as low as 5.2. Two hydrophobic networks responsible for the stability and slow heme dissociation and reorientation in OM cyt bs have been identified. Mutation of the five residues involved in these hydrophobic networks in OM cyt bs yields a protein with the structural elements of Me cyt bs Molecular dynamics simulations predict two conformers of Me cyt bs in solution, a cleft-open and a cleft-closed form and only one, the cleft-closed form, for OM cyt Z>5.3 2 394 is proposed that OM cyt bs is held in the cleft-closed conformation by one of its hydrophobic networks. 

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