Thermodynamic cycle perturbation

Reddy RM, Varney MD, Kalish V, Viswanadhan VN, Appelt K. Calculation of relative differences in the binding free energies of HIV-1 protease a thermodynamic cycle perturbation approach. J. Med. Chem. 1994 37 1145-1152. 

In 1984 (2), the thermodynamic cycle-perturbation method was introduced to help compare the binding affinity of a group of similar inhibitors. This method is based on constructing a thermodynamic cycle relating two binding processes ... 

Figure 6 Thermodynamic cycle—perturbation method for a host interacting with two different guest molecules.

One approach is the thermodynamic cycle-perturbation method that allows one to eompare the relative binding affinity of a number of similar ligands. This approaeh reeognizes the difficulty in simulating the absolute binding affinity AG between a ligand and its receptor ... 

Calculation of Relative Differences in the Binding Free Energies of HFVl Protease Inhibitors A Thermodynamic Cycle Perturbation Approach. 

B. Lesyng and E. F. Meyer, Biopolymers, 30, 773 (1990). Thermodynamic Cycle-Perturbation Study of the Binding of Trifluoroacetyl Dipeptide Anilide Inhibitors with Porcine Pancreatic Elastase. 

The general formalism for thermodynamic simulation methods follows from early work by Zwanzig [33], and provides a tool for the computation of thermodynamic properties, AA, AE and AS, as well as barriers for chemical processes occurring on long timescales [34]. These methods take on several guises in present implementations. The two approaches which we will describe are termed thermodynamic cycle perturbation theory (TP) [35] and thermodynamic integration (TI) [36]. Both of the methods are based on the definition of a hybrid Hamiltonian which represents some mixture of the initial state (1) and final state (2) of the system [37]. If /.represents the coordinate describing the pathway used to interconvert the two systems, then the hybrid Hamiltonian may be defined by [35, 37]. 

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