THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

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It is difficult to calculate the free energy of macromolecules from computer simulations because the entropy cannot be expressed as an equilibrium average. It is shown how one may systematically obtain successive approximations to the entropy using moments of the internal coordinate displacements evaluated from the simulation. A novel stochastic dynamics approach to the evaluation of the thermodynamics properties of quantum systems has been developed. This method is based on the similarity between the classical diffusion equation and the quantum mechanical Bloch equation for the density matrix. It is shown that for several systems, the results obtained using this approach are in good agreement with those based on the eigenvalues obtained by numerically solving the Schrodinger equation. A model for the influence of surface charge on the assembly of hemoglobin has been developed. In this model, the monomers first diffuse together, under the influence of their mutual electrostatic interaction, to form an encounter complex which then rearranges to form stereospecific contacts. This model quantitatively describes the measured association rate constants for the reaction between native Alpha chains and a series of mutant Beta chains having surface charges that differ from the native by plus/minus 1, plus/minus 2 units.