Prediction of the Effect of pH on the Aggregation and Conditional Folding of Intrinsically Disordered Proteins with SolupHred and DispHred

Critical Assessment of pH‐Dependent Lipophilicity Profiles of Small Molecules: Which One Should We Use and In Which Cases?

“…Despite the lack of a consensus formalism to model log D pH as a function of $${P_{{\rm{IP}}}^{{\rm{app}}} }$$ , and considering that different theoretical approaches have shown similar trends, [14,21,22] Equation 2 has been successfully used for modeling the lipophilicity of ionized compounds in many areas of basic and applied sciences. For instance, to study the aggregation of naphthenic acids in aqueous environments with different saline concentrations, [50] in log D pH calculations for lignin derivatives and small datasets of drug‐like compounds in different solvents by QM and statistical thermodynamical methods, [51] partitioning of antioxidants, [52] aquatic hazard assessment of ionizable organic chemicals, [53] sorption mechanisms of antimicrobials in the soil, [54] and physicochemical properties of peptides and proteins [15–18] …”

“…For instance, to study the aggregation of naphthenic acids in aqueous environments with different saline concentrations, [50] in logD pH calculations for lignin derivatives and small datasets of drug-like compounds in different solvents by QM and statistical thermodynamical methods, [51] partitioning of antioxidants, [52] aquatic hazard assessment of ionizable organic chemicals, [53] sorption mechanisms of antimicrobials in the soil, [54] and physicochemical properties of peptides and proteins. [15][16][17][18] A previous study has evaluated predictions of logD pH using Equations 1 and 2 for a small set of 35 ionizable molecules with computed logP N and log P app I values calculated via an extension of the Miertus-Scrocco-Tomassi solvation model. [14] In that work, Equation 1 tends to overestimate the hydrophobicity of the studied molecules, given that the P app IP is not considered, whereas Equation 2 predicts a logD pH value closer to the experimental values.…”

“…This property has been shown to be useful in QSAR models to explain how small molecules have human brain cell permeability [12] or bind to human serum albumin. [13] The logD pH has also been used as an effective predictor of pH-dependent lipophilicity profiles for small molecules [14] and to characterize structural properties in proteins and peptides, such as protein-folding and aggregation, [15] solubility, [16] and antimicrobial activity, [17,18] through pH-dependent lipophilicity scales. [19,20] As an alternative to experimentally determined logD pH values, theoretical lipophilicity profiles provide the opportunity to obtain this descriptor quickly and often with high accuracy.…”

Critical Assessment of pH-Dependent Lipophilic Profiles of Small Molecules for Drug Design: Which One Should We Use and In Which Cases?

“…This property has been shown to be useful in QSAR models to explain how small molecules have human brain cell permeability 12 or bind to human serum albumin 13 . The logDpH has also been used as an effective predictor of pHdependent lipophilicity profiles for small molecules 14 and to characterize structural properties in proteins and peptides, such as protein-folding and aggregation 15 , solubility 16 , and antimicrobial activity 17,18 , through pH-dependent lipophilicity scales. 19,20 As an alternative to experimentally determined logDpH values, theoretical lipophilicity profiles provide the opportunity to obtain this descriptor quickly and often with high accuracy.…”

“…For instance, to study the aggregation of naphthenic acids in aqueous environments with different saline concentrations 50 , in logDpH calculations for lignin derivatives and small datasets of drug-like compounds in different solvents by QM and statistical thermodynamical methods 51 , partitioning of antioxidants 52 , aquatic hazard assessment of ionizable organic chemicals 53 , sorption mechanisms of antimicrobials in the soil 54 , and physicochemical properties of peptides and proteins. [15][16][17][18] Previous studies have evaluated predictions of logDpH using Equations 1 and 2 for a small set of 35 ionizable molecules with computed logPN and logP I app values calculated via an extension of the Miertus-Scrocco-Tomassi solvation model. 14 It has been reported that Equation 1 tends to overestimate the hydrophobicity of the studied molecules, given that the P I app is not considered, whereas Equation 2 predicts a logDpH value closer to the experimental values.…”