Book of Abstracts: Albany 2003
June 17-21 2003
Configurational Entropy Change in Protein-DNA Complexes: Estimates From Molecular Dynamics Trajectories
The role of dynamic, flexible structures and the ensuing vibrational and configurational entropy effects in the thermodynamics of macromolecular association is an issue of significance that calls for attention as our knowledge of the structural properties and their thermodynamic effects buildup. In a recent observation, Jen-Jacobson and coworkers [Structure 8, 1015-1023 (2000)] proposed a model for the thermodynamics of protein-DNA recognition that argues that structurally strained complexes such as the Catabolite Activator Protein (CAP) - DNA system are entropically driven while in contrast, unstrained complexes such as the λ cI repressor-operator system are enthalpically driven. The issue of motional properties in protein-DNA systems and their thermodynamic effects has been studied on the basis of stable molecular dynamics (MD) simulation trajectories of 4 ns or greater length for the λ cI repressor protein - OL1 operator complex and the CAP - DNA complexes and their component unbound forms. The covariances of positional fluctuations during the MD of these units are employed to extract an estimate of the configurational entropy change based on a quasi-harmonic approximation. The results support the proposed relation between the structural features of the complex in solution and the thermodynamic factors favoring complexation. The study also highlights the applicability and usefulness of such simulation based techniques for gaining insights into the dynamic structural properties of such large systems that are otherwise difficult to access.