Conformational Contribution to Thermodynamics of Binding in Protein Complexes Through Microscopic Simulations

Abstract

The biomacromolecular interactions are primarily governed by the conformational changes. We show that the thermodynamics of these conformational changes in biomacromolecular complexes can be extracted from the distributions of the dihedral angles of the macromolecules. These distributions are obtained from the equilibrium configurations generated via all atom molecular dynamics simulations. The conformational thermodynamics data we obtained for the system of calmodulin bound to different peptide complexes using our methodology corroborate well with the experimentally observed conformational and binding entropies. The conformational free energy changes and its contributions for different peptide binding regions of calmodulin are evaluated microscopically. We also extend the histogram based methods for calculation of conformational thermodynamics to calcium ion binding to calmodulin. This gives the microscopic information on the participation of different residues in the metal binding process.