i am calculating free energy of restraint for absolute binding free energy system of protein and ligand. i am confused between standard volume values. standard Volume is 1660A^3 , should i use this value in calculation or the value of the volume of my box after solvation (309.876nm^3)?
Mrs/Miss Saeed,
Your question assumes that you are not fluent with a topic in chemistry, i.e. "chemical thermodynamics".
The free Gibbs energy as thermodynamic parameter expresses energetics of a system at T = const and P = const, but the system is isolated. Which means that it is the exchange of heat and work, but there are not exchanging matter. It expresses energetics of a system towards given chemical content. The energy balance accounts for any kind of interactions/chemical reactions and more, but the content is constant. The interaction scheme can causes for different final 3D state of disposition of your drug and protein molecules. The free Gibbs energy, referred namely the interaction scheme, molecular conformation and 3D assemblies is more preferred at certain system, using the balance on the base on the energy. The initial "volume" in term used in your question is neglected.
I do not know what approach you use studying solvation effects, but if you use 3D molecular dynamic box with a set molecules of the solvent in the presence of your drug-receptor system, as it can be deduced, then I should point out that this model does not express good real drug-receptor interactions. Because of there is unable in the living systems to fix presence of protein molecule within the framework of rigid 3D box and to determine interactions only in this 3D fixed box under ambient conditions (P = 1 atm). Second, there are important close solute-solvent interactions. More suitable is mixed-solvation approach based on few solvent molecules disposed around active loop/molecule, while the rest part of interacting system can be expressed by so-called polarizable continuum approaches (PCMs); i.e. as a structureless continuum where there is taken into account only dielectric properties.
As part of above two paragraphs, can be found as attachment an example of a biomacromolecule, which crystallographic coordinates are taken, computing thermochemical properties. The crystal structure is 2ptc.pdb (Protein Data Bank). It is described only I-chain.
(i) In Fig. 1 (attachment) the crystallographic structure of I-chain (Fig. 1b), MM optimized (Fig. 1a) and MD-optimized (Fig. 1c) ones are shown. As can be seen, MD calculations leads to an almost completely destroying of the real 3D structure of the protein and dispersion of solvent H2O molecules far from protein molecule in 3D space (Fig. 1c). Therefore, MD analysis not realistically expresses the experimental 3D crystallographic data, involving solvent molecules close to the protein surface. Even if you are working with fixed box volume, MD leads to dispersion of the solvent molecules and thus your system is not "isolated" as mentioned above.
(ii) The potential energies of both MM and crystallographic states are negative, and increasing in stability occurs. The MD computations cause for increasing in the energy, and thus to a decreasing of it stability (Fig. 2).
(iii) The thermochemistry data (gas-phase) obtained for the I-chain show:
Temperature = 298.15 K
Pressure, P = 101325.00 Pa
Number of atoms 486
MW = 6583.4974
Stoichiometry - C284N84O111S7
Utot = 7.437 kJ/mol 1.777 kcal/mol
Htot = 9.916 kJ/mol 2.370 kcal/mol
Stot = 430.537 J/K/mol 102.901 cal/K/mol
Gtot = -118.449 kJ/mol -28.310 kcal/mol
The vibrational contribution is neglected.
Experimentally, there are found free Gibbs energy values for the whole protein (E+I chains) within the range (-0.2) to (+8) kcal.mol-1. You should bear in mind that the PCMs energies fit better to the experimental quantities of such systems, especially these exhibiting a high polarity, then the gas-phase computations.
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