Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: Relative free energies for a series of not too different compounds can be estimated accurately from a single simulation of an unphysical reference state that encompasses the characteristic molecular features of the compounds. Previously, this method has been applied to the calculation of free energies of solvation and of ligand binding for small molecules. In the present study  investigate the limits to the accuracy of the method by applying it to a realistic model of the binding of a set of rather large ligands to the protein factor Xa, a key protein in current efforts to design anticoagulation drugs. The evaluation of the binding free energies and conformations of nine derivatives of a biphenylamidino inhibitor leads to insights regarding the effect of the size, flexibility, and character of the unphysical part of the ligand in the reference state on the accuracy of the predicted binding free energies.
['Chris Oostenbrink', 'Wilfred F. van Gunsteren']
I am writing a research paper on a idea Single‐step perturbations to calculate free energy differences from unphysical reference states: Limits on size, flexibility, and character
[{"from": "human", "value": "I am writing a research paper on a idea Single\u2010step perturbations to calculate free energy differences from unphysical reference states: Limits on size, flexibility, and character"}, {"from": "gpt", "value": "Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: Relative free energies for a series of not too different compounds can be estimated accurately from a single simulation of an unphysical reference state that encompasses the characteristic molecular features of the compounds. Previously, this method has been applied to the calculation of free energies of solvation and of ligand binding for small molecules. In the present study  investigate the limits to the accuracy of the method by applying it to a realistic model of the binding of a set of rather large ligands to the protein factor Xa, a key protein in current efforts to design anticoagulation drugs. The evaluation of the binding free energies and conformations of nine derivatives of a biphenylamidino inhibitor leads to insights regarding the effect of the size, flexibility, and character of the unphysical part of the ligand in the reference state on the accuracy of the predicted binding free energies."}]