Structure and free energy of complex thermodynamic systems

Abstract

Biological systems are intrinsically complex, involving many degrees of freedom, heterogeneity, and strong interactions among components. For the simplest of biological substances, e.g., biomolecules, which obey the laws of thermodynamics, we may try to investigate them by means of a statistical mechanical approach. Even for these simplest many-body systems, assuming all microscopic interactions are completely known, current physical and chemical methods of characterizing the overall structure and free energy face the fundamental challenge of an exponential amount of computations as the number of degrees of freedom of these systems increases. As a response to this problem, two general procedures have been developed to compute the structure (Monte Carlo-minimization method) and free energy (Monte Carlo recursion method) of a complex thermodynamic system. The Monte Carlo-minimization procedure has been applied to determine the structure of a pentapeptide Met-enkephalin, leading consistently to a stable β-bend structure, starting from random initial conformations. The Monte Carlo recursion method has been applied to a Lennard-Jones fluid, with results in agreement with previously published values of the free energy obtained from other procedures.