Talk:Implicit solvation

message: There is a problem with electrostatic models, such as PB, GB, or GBSA, when they are applied to proteins with ionizable residues.  If a charged residue (Asp, for example) is transfred from water to a nonpolar media (such as membrane or protein interior), this would be eneretically very costly according to calculations with GB, for example. However in the real life, this residue will simply becomes uncharged, which costs very little, 2.3RT(pH-pK), as has actually been observed for protein mutants with buried ionizable residues and hydrophobic alpha-helical peptides in membranes with a single ionizable residue in the middle. If I understand correctly, such ionization effects are not included in PB, GB, or GBSA. As a result, the energies calculated with  PB, GB, or GBSA will be grossly overestimated.  Do you agree? And if you do, should this be mentioned? Biophys 22:04, 31 October 2006 (UTC)
replies: text: This sounds very interesting. Do you have a paper reference that talks about this? Jorgenumata 09:44, 1 November 2006 (UTC)
replies: text:  Yes, there are references. I will add some text with the referenences later. Biophys 13:17, 1 November 2006 (UTC)
thread_title: A problem with electrostatic implicit solvation models

message: The initial version of the implicit solvation model was to use different solvation parameters for different types of atoms (not the "uniform" value of 40 cal/mol/A for all atoms including N or O), and include some electrostatic contributions only for ionizable groups. For example, such approach was implemented in FANTOM. I think this should be described. Biophys 01:10, 1 November 2006 (UTC)
replies: text: This is addressed. Look at the section "Ad-hoc fast solvation models". It says that A first generation of fast implicit solvents is based on the calculation of a per-atom solvent accessible surface area. For each of group of atom types, a different parameter scales its contribution to solvation.  It then goes on to explain the second generation, like Karplus Lazaridis EEF1. If you have specific information about FANTOM, please include it. Jorgenumata 09:43, 1 November 2006 (UTC)
replies: text:  Yes, I see. The text you have written is very good. I just would like to say more about solvation models in the Eisenberg-McLachlan style. Also, such models can be applied for different puproses, such as modeling of protein folding or modeling of protein-membrane interactions. So, more can be said about certain practical applications (one of them FANTOM), with the corresponding references. I will make some additions that you are welcome to edit (may be next week). Biophys 13:15, 1 November 2006 (UTC)

text:  I also have a question. What reference says that Poisson-Boltzmann equation belongs to implicit solvation models? I am not sure this is right. Biophys 13:27, 1 November 2006 (UTC)
replies: text: That's not all the PB equation can be used for, but it is definitely used as an implicit solvent model - see this paper for an example. Opabinia regalis 04:56, 2 November 2006 (UTC)

text: Thank you!  I thought this equation might be represented by a separate Wikipedia article, since it is multi-purpose.  But this is not really important. Biophys 23:41, 2 November 2006 (UTC)
replies: text: Actually it also has its own article - Poisson-Boltzmann equation. It's pretty stubby right now though - it didn't even have the equation in it till recently. Opabinia regalis 01:12, 3 November 2006 (UTC)
thread_title: "Old-fashion" implicit solvation model

message: I can try to write down something about limitations of the implicit solvation models. Such limitations are important to know.Biophys 01:10, 1 November 2006 (UTC)
replies: text: That would be useful. I never use implicit solvent but I'm actually pretty impressed with the quality of the results some people report, considering how bad the approximation should be. Opabinia regalis 01:12, 3 November 2006 (UTC)
replies: text:  Good comment! This method may work well because derivation of atomic solvation parameters from experimental transfer free energies (say water-cyclohexane) of organic compounds is very straightforward.  Therefore, implicit models can capture energetics of solvations (with all its hidden entropic contributions) much better than MM or MD with all their serious defficiencies (see what I have written about that in force fields) (so the "implicit solvation" is not to save the computational time, this is an alternative approach). However, there are two things to remember. First, these solvation parameters must be properly determined (taking ad hoc values of 20 or 40 cal/mol/A2 for all atoms including C, N,... is not a good parameterization; and the interior of proteins and membranes is not wet octanol). Second, such parameters should be applied only to describe solvation or transfer of atoms between uniform media. One can express van der Waals attractions in solid state in surface enegy units or volume energy units, but this approximation is too crude (it does not capture "specific" distance-dependent interactions which are responsible for clustering of groups with similar polarities in protein structures). Biophys 17:03, 4 November 2006 (UTC)
thread_title: Problems and limitations

message: If the generalized Born model "does not include entropic effects" then why is it stated as ΔG and not an enthalpy?
Ggrieves 17:54, 25 July 2007 (UTC)
replies: text: Good question! The original Poisson-Boltzmann equation icludes only electrostatic energy (a part of enthalpic component). However "Gs" appears in the next equation (Generalized Born). This is because people who are doing this trick often claim to calculate free energy, although actually they do not. In addition, they are trying to combine electrostatic energy with empirical free energy of solvation calculated using first equation (deltaASA formula). I personally think that PB and GB models are only good to create an impression of "good science" and prefer the simplest ASA-model, because it actually works if properly parameterized (within certain limits as everything). If you want to improve this article, you are very welcome.Biophys 20:07, 25 July 2007 (UTC)
replies: text: PB and GB model the electrostatic free energy, which includes an entropic component. However, this is not the whole configurational entropy of the water. PB and GB are mean-field approaches which do not account for directional interactions with the solute that alter configurational freedom. At room temperature, the hydrophobic effect is mostly due to a change in this kind of entropy, and is thus not included. It has been known for many decades that the hydrophobic effect is the most important driving force for protein folding. It is thus a strange state of affairs that the modeling community has devoted so much effort to electrostatics and neglected entropy and the hydrophobic effect. I agree with Biophys that PB is sometimes abused. It is used to give the impression that a complete free energy was calculated, when in fact only part of it was estimated. Jorgenumata 11:01, 11 October 2007 (UTC)
thread_title:  Question for the Experts 

message: To Implicit solvent models ? Biophys (talk) 13:45, 12 June 2011 (UTC)
replies: text: Sounds better. • Jesse V.(talk) 06:29, 20 August 2012 (UTC)
thread_title: Rename?