Lipophilicity in Drug Design: An Overview of Lipophilicity Descriptors in 3D-QSAR Studies

Ginex, Tiziana; Vázquez, Javier; Gilbert, Enric; Herrero, Enric; Luque, F. Javier

doi:10.4155/fmc-2018-0435

Cited by 39 publications

(38 citation statements)

References 96 publications

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“…Under the same framework, our group has recently presented a 3D similarity scheme to enrich the docking performance based on the usage of lipophilic descriptors [ 168 ] determined from quantum mechanical-based continuum solvation models [ 80 ]. The 3D similarity was determined by comparing the 3D distribution of atomic lipophilicity computed by PharmScreen [ 31 , 169 ] ( Figure 8 ), and the similarity measurements were exploited in conjunction with the poses obtained by using three docking programs: Glide, rDock [ 170 ], and GOLD [ 171 ].…”

Section: Hybrid Approachesmentioning

confidence: 99%

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Vázquez

Lopez

Gibert³

et al. 2020

Molecules

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124

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Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued efforts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature.

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Section: Hybrid Approachesmentioning

confidence: 99%

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Vázquez

Lopez

Gibert³

et al. 2020

Molecules

Self Cite

124

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“…Lipophilicity is a crucial physicochemical property to understand the biological and pharmaceutical properties of drugs, as it reflects the differential solubility of solutes in aqueous and organic environments [1][2][3][4]. Generally, the lipophilicity is estimated from the partitioning of compounds between aqueous and n-octanol phases [5][6][7], which have been also used as reference systems in the development of a variety of computational approaches [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Prediction of the n-octanol/water partition coefficients in the SAMPL6 blind challenge from MST continuum solvation calculations

Zamora

Pinheiro

German

et al. 2019

J Comput Aided Mol Des

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The IEFPCM/MST continuum solvation model is used for the blind prediction of noctanol/water partition of a set of 11 fragment-like small molecules within the SAMPL6 Part II Partition Coefficient Challenge. The partition coefficient of the neutral species (log P) was determined using an extended parametrization of the B3LYP/6-31G(d) version of the Miertus-Scrocco-Tomasi continuum solvation model in n-octanol. Comparison with the experimental data provided for partition coefficients yielded a root-mean square error (rmse) of 0.78 (log P units), which agrees with the accuracy reported for our method (rmse = 0.80) for nitrogencontaining heterocyclic compounds. Out of the 91 sets of log P values submitted by the participants, our submission is within those with an rmse < 1 and among the four best ranked physical methods. The largest errors involve three compounds: two with the largest positive deviations (SM13 and SM08), and one with the largest negative deviations (SM15). Here we report the potentiometric determination of the log P for SM13, leading to a value of 3.62 ± 0.02, which is in better agreement with most empirical predictions than the experimental value reported in SAMPL6. In addition, further inclusion of several conformations for SM08 significantly improved our results. Inclusion of these refinements led to an overall error of 0.51 (log P units), which supports the reliability of the IEFPCM/MST model for predicting the partitioning of neutral compounds.

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“…Prediction of Δ solv G ∘ in nonaqueous solvents is necessary in order to predict partition coefficients between different solvents. The octanol/water partition coefficient (equilibrium constant K ow ), in particular, is a common measure of lipophilicity (or conversely, hydrophobicity), [456][457][458] and is related to solvation energies according to…”

Section: Smx and Other Sasa-based Modelsmentioning

confidence: 99%

Section: Smx and Other Sasa-based Modelsmentioning

confidence: 99%

“…The value of K ow is widely used in drug-discovery applications, [458][459][460] and atomic decomposition of terms contributing to ΔΔG ∘ in Equation (4.11) has been used to determine similarity indices for predicting quantitative structure-activity relationships. 458 For environmental toxicology purposes, K ow is an important physical parameter to determine for any new compound. 461 The octanol/water partition coefficient was the subject of a recent blind challenge for theoretical methods, 462 with the SMx models emerging as amongst the best performers with a root-mean-square error of 0.44 in units of log 10 K ow .…”

Section: Smx and Other Sasa-based Modelsmentioning

confidence: 99%

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Dielectric continuum methods for quantum chemistry

Herbert

2021

WIREs Comput Mol Sci

136

195

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This review describes the theory and implementation of implicit solvation models based on continuum electrostatics. Within quantum chemistry this formalism is sometimes synonymous with the polarizable continuum model, a particular boundary‐element approach to the problem defined by the Poisson or Poisson–Boltzmann equation, but that moniker belies the diversity of available methods. This work reviews the current state‐of‐the art, with emphasis on theory and methods rather than applications. The basics of continuum electrostatics are described, including the nonequilibrium polarization response upon excitation or ionization of the solute. Nonelectrostatic interactions, which must be included in the model in order to obtain accurate solvation energies, are also described. Numerical techniques for implementing the equations are discussed, including linear‐scaling algorithms that can be used in classical or mixed quantum/classical biomolecular electrostatics calculations. Anisotropic models that can describe interfacial solvation are briefly described. This article is categorized under: Electronic Structure Theory > Ab Initio Electronic Structure Methods Molecular and Statistical Mechanics > Free Energy Methods

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Lipophilicity in Drug Design: An Overview of Lipophilicity Descriptors in 3D-QSAR Studies

Cited by 39 publications

References 96 publications

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Prediction of the n-octanol/water partition coefficients in the SAMPL6 blind challenge from MST continuum solvation calculations

Dielectric continuum methods for quantum chemistry

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