ALOGPS

Computed
QSAR

CCM15

Computed
Q-based

COSMOmic 15

COSMOmic describes micelles or biomembranes as liquid layers. COSMOmic provides detailed information about the distribution of neutral and ionic species in micellar systems and biomembranes based on the structures obtained from molecular dynamics simulation of membranes and micelles. 

Key features of COSMOmic

  • Partition coefficients in micellar systems
  • Solute distribution profiles along membrane normal 
  • Free energy profile through the membrane or the micelle
  • Neutral and ionic solutes treated on equal footing
  • Spherical, cylindrical and lamellar micelles
  • http://www.cosmologic.de/products/cosmomic.html

  • A. Klamt, U. Huniar, S. Spycher, J. Keldenic: COSMOmic: A Mechanistic Approach to the Calculation of Membrane-Water Partition Coefficients and Internal Distributions within Membranes and Micelles. J. Phys. Chem. B 2008, 112, 12148–12157, DOI: 10.1021/jp801736k

  • S. Jakobtorweihen, T. Ingram, and I. Smirnova: Combination of COSMOmic and molecular dynamics simulations for the calculation of membrane-water partition coefficients. J. Comput. Chem. 2013, 34, 1332-1340, DOI: 10.1002/jcc.23262

  • M. Paloncýová, R.DeVane, B. Murch, K. Berka, and M. Otyepka: Amphiphilic Drug-Like Molecules Accumulate in a Membrane below the Head Group Region. J. Phys. Chem. B, 2014, 118(4), 1030–1039, DOI: 10.1021/jp4112052

  • T. Ingram, S. Storm, L. Kloss, T. Mehling, S. Jakobtorweihen and I. Smirnova: Prediction of Micelle/Water and Liposome/Water Partition Coefficients Based on Molecular Dynamics Simulations, COSMO-RS, and COSMOmic. Langmuir, 2013, 29(11), 3527–3537, DOI: 10.1021/la305035b

CCM18

Computed
Q-based

COSMOmic/COSMOperm 18

COSMOmic describes micelles or biomembranes as liquid layers. COSMOmic provides detailed information about the distribution of neutral and ionic species in micellar systems and biomembranes based on the structures obtained from molecular dynamics simulation of membranes and micelles. COSMOperm adds fast calculation of diffusion profile, which in addition to free energy profile allows estimation of the membrane permeability. 

Key features of COSMOmic

  • Partition coefficients in micellar systems
  • Solute distribution profiles along membrane normal 
  • Free energy profile through the membrane or the micelle
  • Neutral and ionic solutes treated on equal footing
  • Spherical, cylindrical and lamellar micelles

Key features of COSMOperm

  • Local diffusion coefficients
  • Resistance profiles
  • Intrinsic passive membrane permeabilities
  • pH dependence of permeation
  • http://www.cosmologic.de/products/cosmomic.html

  • A. Klamt, U. Huniar, S. Spycher, J. Keldenic: COSMOmic: A Mechanistic Approach to the Calculation of Membrane-Water Partition Coefficients and Internal Distributions within Membranes and Micelles. J. Phys. Chem. B 2008, 112, 12148–12157, DOI: 10.1021/jp801736k

  • A. Klamt, M. Diedenhofen. A Refined Cavity Construction Algorithm for the Conductor-like Screening Model. J Comp. Chem. 2018, DOI: 10.1002/jcc.25342

CPapp

Experimental
Permeability

Mechanistic model describing apparent permeabilities (Papp) based on different resistances solutes encounters when permeationg a cell monolayers. Moled is taking account a cytosolic, paracellular and lateral pathway with different resistances to a solute. The final Papp is than derived describing apparent cell permeability through Caco-2/MDCK cell monolayer at pH 7.4.

Bittermann K, Goss K-U (2017) Predicting apparent passive permeability of Caco-2 and MDCK cell-monolayers: A mechanistic model. PLoS ONE 12(12): e0190319. https://doi.org/10.1371/journal.pone.0190319

CPMM

Computed
Mechanistic

PerMM model

Permeability of Molecules across Membranes is calculated by PerMM server and database.

The underlying thermodynamics-based method calculates membrane binding affinity, energy profiles along the bilayer normal, and permeability coefficients of diverse molecules across different membranes. Calculated permeability coefficients reproduce experimental data for model membrane systems, such as BLM (R2 = 0.9) and PAMPA (R2 = 0.6).

The method operates with atomic 3D structures of molecules and represents anisotropic properties of lipid bilayers of different composition by transbilayers profiles of dielectric and hydrogen-bonding capacity parameters. These profiles have been derived for several artificial and natural membranes from distributions of lipid groups and from surface hydrophobicity of membrane proteins along the bilayer normal.

  • http://permm.phar.umich.edu

  • A.L. Lomize, I.D. Pogozheva, H.I. Mosberg: Anisotropic solvent model of the lipid bilayer. 2. Energetics of insertion of small molecules, peptides, and proteins in membranes. J. Chem. Inf. Model. 51, 930-946, 2011. DOI: 10.1021/ci200020k

  • A.L. Lomize, I.D. Pogozheva: Prediction of passive membrane permeability and translocation pathways of biologically active molecules. Biophys. J. 112(3) Supp1, 525a, 2017.  DOI: 10.1016/j.bpj.2016.11.2838

  • A.L. Lomize, I.D. Pogozheva: Physics-Based Method for Modeling Passive Membrane Permeability and Translocation Pathways of Bioactive Molecules. J. Chem. Inf. Model. 2019, 59, 3198-3213, 2019. DOI: 10.1021/acs.jcim.9b00224

CQikProp

Computed
QSAR

QikProp predicts the widest variety of pharmaceutically relevant properties - octanol/water and water/gas log Ps, log S, log BB, overall CNS activity, Caco-2 and MDCK cell permeabilities, log Khsa for human serum albumin binding, and log IC50 for HERG K+-channel blockage - so that decisions about a molecule's suitability can be made based on a thorough analysis. QikProp bases its predictions on the full 3D molecular structure; unlike fragment-based approaches, QikProp can provide equally accurate results in predicting properties for molecules with novel scaffolds as for analogs of well-known drugs. QikProp computes over twenty physical descriptors, which can be used to improve predictions by fitting to additional or proprietary experimental data, and to generate alternate QSAR models.

Schrödinger Release 2020-3: QikProp, Schrödinger, LLC, New York, NY, 2020.

CVOLSURF

Computed
QSAR

A classical quantitative structure–activity relationship (QSAR) approach with simple physicochemical parameters and 3D-QSAR, VolSurf.

M. Fujikawa, R. Ano, K. Nakao, R. Shimizu, M. Akamatsu, Relationships between structure and high-throughput screening permeability of diverse drugs with artificial membranes: Application to prediction of Caco-2 cell permeability. Bioorganic & Medicinal Chemistry,13 (15) 2005, 4721-4732

DC-DMR

Experimental
Permeability

Diffusion-controlled water permeation across bilayers of polyunsaturated phospholipids measured by 17O nuclear magnetic resonance. 

Huster D, Jin AJ, Arnold K, Gawrisch K.: Water permeability of polyunsaturated lipid membranes measured by 17O NMR. Biophys J, Volume 73 (2), 855-864, 1997.

EBAMP

Experimental
Permeability

Bio-mimetic Artificial Membrane Permeation Assay

Bio-mimetic Artificial Membrane Permeation Assay (BAMPA) is the modification of PAMPA. In BAMPA assay the lipid composition mimics intestinal brush border membrane.

Sugano K., Takata N., Machida M., Saitoh K.,  Terada K.: Prediction of passive intestinal absorption using bio-mimetic artificial membrane permeation assay and the paracellular pathway model. Int. J. Pharm., 241, 241–251, 2002.

EBLM

Experimental
Permeability

Black lipid membrane

Experimental system of lipids assembled on thin layer of hydrophobic solvent such as decane or squalene surrounded by two aqueous environments in the small aperture from hydrophobic material such as Teflon. Small layer of solvent rests in the middle of newly formed membrane - hence the name black in reflected light. This model membrane can be used for measurement of permeabilities.

  • S.H. White: Analysis of the torus surrounding planar lipid bilayer membranes. Biophys. J. 12 (4), 432–445, 1972. DOI: 10.1016/s0006-3495(72)86095-8

ECACO

Experimental
Permeability

Caco-2 permeability assay

Caco-2 is a well-established cell line derived from human colon carcinoma. Upon cultivation, the cells spontaneously differentiate into monolayers of polarised enterocytes. Caco-2 cells are widely used as an in vitro model for predicting human drug absorption. The permeability can be determined with LC-MS.

  • I.J. Hidalgo, T.J. Raub, R.T. Borchardt: Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology, 96, 736-749, 1989--the backstory.

ECALU3

Experimental
Permeability

Calu-3 is a well-established cell line derived from human lung cancer cells (bronchial submucosal gland carcinoma). Upon cultivation, the cells spontaneously differentiate into adherent monolayers. Calu-2 cells are widely used as both in vitro and in vivo models for predicting human drug absorption and in drug development against lung cancer.

ECFM

Experimental
Positioning

Confocal Fluorescence Microscopy

Confocal fluorescent microscopy eliminates the light collected from the sample which is out of focus. It has a pinhole on both the excitation and emission light paths. The fluorescence confocal microscope has the advantage that photobleaching is reduced.

Peter Jomo Walla, Modern Biophysical Chemistry, Wiley: Weinheim, 2014

 

 

EEPR

Experimental
Partitioning

Electron paramagnetic resonance (EPR) is spectroscopic method that is capable of analyze surrounding(microenvironment) of paramagnetic molecules such as nitroxide radicals. One of typical nitroxide radical-based EPR probes is EMPO(2,2,6,6-tetramethylpiperidine-1-oxy that enables to study membrane systems. This technique can be used to measure partitionig of nitroxide radical into hydrophilic/lipophilic environment of membranes.

Elpelt A, Ivanov D, Nováčková A, Kováčik A, Sochorová M, Saeidpour S, Teutloff C, Lohan SB, Lademann J, Vávrová K, Hedtrich S, Meinke MC.: Investigation of TEMPO partitioning in different skin models as measured by EPR spectroscopy - Insight into the stratum corneum. J Magn Reson, Volume 310, 106637, 2020

EFALUV

Experimental
Permeability

Artificial large unilamellar vesicle (LUV) permeabilities were determined by monitorinf concentracion-dependent or pH-sensitive quenching of entraped carboxyfluorescein on a stopped-flow fluorimeter.

Lande MB, Donovan JM, Zeidel ML.: The relationship between membrane fluidity and permeabilities to water, solutes, ammonia, and protons. J Gen Physiol, Volume 106 (1), 67-84, 1995

EFCS

Experimental
Positioning

Fluorescence Correlation Spectroscopy

Fluctuations of the fluorescence signals caused by the diffusion of labelled biomolecules in and out of the confocal detection focus are evaluated. It is therefore used to determine the average number of individual fluorescently labelled biomolecules in the confocal volume, and to get access to the average size- and viscosity-dependent diffusional time in which the fluorophores diffuse through the detection volume.

EFDC

Experimental
Permeability

 Franz Diffusion cell

One of the most common techniques for measuring absorption in vitro is the application of the test substance in an appropriate formulation (may be radiolabeled) to the surface of a membrane (skin, artificial membrane...), which is mounted as a barrier between the donor compartment and the receptor compartment of a diffusion cell. Diffusion cells may be of static or flow-through.

 Static diffusion cells sample this chamber and replace it with new perfusate at each time point. Flow-through cells use a pump to pass perfusate through the receptor chamber and collect flux by repeatedly collecting perfusate.


 

  • Bartosova, L. & Bajgar, J. Transdermal drug delivery in vitro using diffusion cells. Curr. Med. Chem. 19, 4671–7 (2012).
  • Kanfer, I., Rath, S., Purazi, P. & Mudyahoto, N. A. In vitro release testing of semi-solid dosage forms. Dissolution Technol. 24, 52–60 (2017).
  • http://www.ses-analysesysteme.de/SES-Franz_Cell_inline_uk.htm

EGUV-CCD

Experimental
Permeability

We describe a technique for determining the permeability of a phospholipid membrane of micrometre-sized giant unilamellar vesicle (GUVs) from a sequence of videomicrographs, which complements the existing methods of determining membrane permeability on either sub-micrometre-sized liposomes (SUV, LUV) or planar membranes. The technique relies on determining the radius of a spherical GUV with great precision, and offers a substantial improvement over similar techniques which rely on quantifying the properties of the phase-contrast halo such as the height or width of its profile.

Peterlin, P., Gasper. J., Pisanski, T. Determining membrane permeability of giant phospholipid vesicles from a series of videomicroscopy images. 2009. Meas. Sci. Technol. 20, 7pp

ELFA

Experimental
Permeability

Liposomal fluorescence assay

This method is capable to determine permeation kinetics of basic drug-like solutes across lipid bilayers. The assay is based on the hypothesis that permeation of a weak base along a concentration gradient results in net proton release at the cis-side and net proton capture at the trans-side of the bilayer. Proton release by the basic small molecule occurs prior to membrane permeation, and proton uptake occurs after permeation. The resulting pH changes are monitored with pH-sensitive fluorophores.

K. Eyer, F. Paech, F. Schuler, P. Kuhn, R. Kissner, S. Belli, P.S. Dittrich, S.D. Krämer: A liposomal fluorescence assay to study permeation kinetics of drug-like weak bases across the lipid bilayer. J Control Release. 2014 Jan 10;173:102-9. doi: 10.1016/j.jconrel.2013.10.037

EMDCK

Experimental
Permeability

MDCK (Madin Darby Canine Kidney) permeability assay is one of drug absorption screening methods. Compared to Caco-2 cells, MDCK cells can form cell monolayer with tight junction much faster, with lower transporters expression and metabolic activities.

ENMRD

Experimental
Permeability

The diffusive permeability to water molecules of lipid vesicle swith entrapped para-magnetic solute ions determined from analysis of the magnetic field dependence (nuclear magnetic relaxation dispersion, or NMRD profile) of T I of exterior solvent water protons.

Koenig SH, Ahkong QF, Brown RD, Lafleur M, Spiller M, Unger E, Tilcock C.: Permeability of liposomal membranes to water: results from the magnetic field dependence of T1 of solvent protons in suspensions of vesicles with entrapped paramagnetic ions. Magn Reson Med, Volume 23 (2), 275-286, 1992

EPAM

Experimental
Permeability

Parallel Artificial Membrane Permeability Assay

Experimental method that allows to measure permeability from donor compartment through artificial membrane into an acceptor compartment. After an incubation period the membrane is separated and the amount of compound is measured in both compartments. Hence it is possible to calculate how much drug remained in the membrane.

  • G. Ottaviani, S. Martel, P.-A. Carrupt: Parallel Artificial Membrane Permeability Assay: A New Membrane for the Fast Prediction of Passive Human Skin Permeability. J. Med. Chem. 49 (13): 3948–3954. 2006. DOI: 10.1021/jm060230+
  • M. Kansy, F. Senner, K. Gubernator: Physicochemical high throughput screening: parallel artificial membrane permeability assay in the description of passive absorption processes. J. Med. Chem. 41: 1007–1010, 1998.

EPFQ

Experimental
Positioning

Parallax fluorescence quenching

Parallax analysis of fluorescence quenching can be used to determine the positions of the fluorescent probes within the membrane. Next to the dye, quenchers are used. The position of the dye is calculated by referring to the fluorescence of intensity of the dye in the presence of quencher, to the distance of the quencher from the bilayer center, and to the surface concentration of the quencher.

 

Chattopadhyay, A.; London, E. Biochemistry 1987, 26, 39-45.

Abrams, F. S.; London, E. Biochemistry 1993, 32, 10826-10831.

EPHT

Experimental
Partitioning

pH-metric titration method

pH-metric titration method is used to determine the partitioning coefficient of ionizable compounds. Octanol-water (liposome-water) partition coefficients of ionizable compounds depend on aqueous pKa of compounds measured in the first step of potentiometric titration (or from literature). The second measurement is held in the presence of water-saturated octanol (water-liposome) where the partitioning occurs.

EPS

Experimental
Permeability

Perfusion system

One of the most common techniques for in situ, in vivo or in vitro measurement of drug permeability.   

ESPME

Experimental
Partitioning

Solid-Phase Microextraction

Negligible depletion solid-phase microextraction (SPME) is used to determine free fractions of chemicals in aquatic environments. SPME measures only the freely dissolved fraction in the aqueous environment. SPME can determine partition coefficients between dissolved organic compounds and water. SPME is a good technique to determine bioavailable concentrations of hydrophobic chemicals in aquatic environments.

ESSM

Experimental
Positioning

Steady-state measurements

Steady-state measurements are performed to get insight into the absorption and emission spectra of the investigated compounds.

 

ETRFES

Experimental
Positioning

Time-resolved fluorescence emission spectroscopy

P. J. Walla, "Modern Biophysical Chemistry", Second edition, Wiley, Weinheim, 2014

EUC

Experimental
Permeability

Ussing chamber

An Ussing chamber is an apparatus for measuring epithelial membrane properties. The technique is used to measure the short-circuit current as an indicator of net ion transport taking place across an epithelium.

ITC

Experimental
Partitioning

Isothermal Titration Calorimetry (ITC) is used to directly measure changes of enthalpy upon titration of lipid vesicles into solution of studied compound. Partition coefficients can be calculated from thermodynamical parameters obtained from titration measurements.

Zhang N, Qi R, Chen Y, Ji X, Han Y, Wang Y.: Partition of Glutamic Acid-Based Single-Chain and Gemini Amphiphiles into Phospholipid Membranes. Langmuir, Volume 34 (45), 13652-13661, 2018

MA-GUV

Experimental
Permeability

Micropipette aspiration was used to test mechanical strength and water permeability of giant-fluid bilayer vesicles (GUVs) composed of polyunsaturated phosphatidylcholine PC lipids. The unique feature of the method is that it provides direct observation of water filtration across a sin-gle solvent-free and unsupported bilayer, which can beeasily analyzed to obtain the coefficient for bilayer permeability to water.

Olbrich K, Rawicz W, Needham D, Evans E.: Water permeability and mechanical strength of polyunsaturated lipid bilayers. Biophys J, Volume 79 (1), 321-327, 2000

MDA14A99

Simulated
Atomistic MD

Molecular dynamics simulation with AMBER Lipid14 and AMBER ff99SB

AMBER Lipid14 is the latest force field from AMBER Lipid force fields family, allowing membrane simulation without the need of using additional surface tension. This version of the force field was tested on six different lipid membrane types and is compatible with AMBER protein, nucleic acid, carbohydrates and small molecules force field.

AMBER ff99SB is an all atom (AA) force field with reparametrized phi/psi dihedral terms in energy funcion to better represent secondary structure elements of protein backbone.

  • V. Hornak et al. Comparison of multiple AMBER force fields and development of improved protein backbone parameters. Proteins., 2006, 65(3), 712-725, DOI: 10.1002/prot.21123

  • C. J. Dickson et al. Lipid14: The Amber Lipid Force Field. JCTC 2014, 10(2), 865-879 DOI:10.1021/ct4010307

MDABFC36

Simulated
Atomistic MD

ABF algorithm with CHARM36

ABF algorithm relies on the integration of the average force exerted along the transition coordinate.

CHARMM36 is an all atom (AA) force field for lipid simulation with redefined parameters for lipid headgroups (choline and ethanolamine) and both saturated and unsaturated lipid chains based on quantum mechanical and experimental data. Newly derived parameters were tested on fully hydrated bilayers. Parameters for sphingolipids were added.

MDC36

Simulated
Atomistic MD

CHARMM36 is an all atom (AA) force field for lipid simulation with redefined parameters for lipid headgroups (choline and ethanolamine) and both saturated and unsaturated lipid chains based on quantum mechanical and experimental data. Newly derived parameters were tested on fully hydrated bilayers. Parameters for sphingolipids were added.

  • J. B. Klauda et al. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J. Phys. Chem. B. 2010, 114, 7830-7843 DOI: 10.1021/jp101759q

  • R. M. Venable et al. CHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature. Biophys. J. 2014, 107(1), 134-45, DOI: 10.1016/j.bpj.2014.05.034

MDCG

Simulated
Coarse grain MD

Method based on high-throughput coarse-grained (HTCG) simulations to derive a permeability surface in terms of two simple molecular descriptors—bulk partitioning free energy and pKa.

Menichetti R., Kanekal K. H., Bereau T.: Drug–Membrane Permeability across Chemical Space. ACS Cent, Sci. 5 (2), 290-298, 2019 https://doi.org/10.1021/acscentsci.8b00718

MDCH27

Simulated
Atomistic MD

CHARMM 27 Force field

CHARMM 27 is an all-atom CHARMM forcefield with newly evaluated parameters for  proteins. In the determination of the parameters, self-consistent approaches have been used designed to achieve a balance between the internal (bonding) and interaction (nonbonding) terms and among the solvent-solvent, solvent-solute, and solute-solute interactions. In combination with the general
CHARMM all-atom parameters for nucleic acids and lipids, CHARMM27 provides a consistent set for condensed-phase simulations of a wide variety of molecules of biological interest.

 

A.D. MacKerell, D. Bashford, M. Bellott, R.L. Dunbrack, J.D. Evanseck, M.J. Field, S.
Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F.T.K. Lau,
C. Mattos, S. Michnick, T. Ngo, D.T. Nguyen, B. Prodhom, W.E. Reiher, B. Roux, M.
Schlenkrich, J.C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiorkiewicz-Kuczera, D.
Yin, M. Karplus, All-atom empirical potential for molecular modeling and
dynamics studies of proteins, J. Phys. Chem. B 102 (1998) 3586–3616.

MDD

Simulated
Hybrid

Diffusion across a membrane is first-order (dependent on the concentration of compound but not other species), the permeability coefficient can be calculated readily from unrestrained molecular dynamics simulations. 

Dotson RJ, Pias SC.: Reduced Oxygen Permeability upon Protein Incorporation Within Phospholipid Bilayers. Adv Exp Med Biol, Volume 1072, 405-411, 2018

MDDMM

Simulated
Hybrid

Dynamic Mechanistic Model with MD-Derived Kinetic Rate Constants

The dynamic mechanistic model breaks the permeation process down into steps, with overall permeation being determined by the kinetic rate constants linking each stage in the event. The dynamic model allows incorporation of concentration differences at each position and the surface area to volume ratios.

The method takes for input the free energy landscape calculated for the movement of each molecule across the membrane. It takes three rate constants, which are proportional to the ΔGflip and ΔGmem barriers encountered on the free energy landscape. In this model of permeation, movement between each position depends not only on the kinetic rate constants linking compartments but also the concentration of small molecule in each compartment.

C.J. Dickson, V. Hornak, R.A. Pearlstein, J.S. Duca: Structure−Kinetic Relationships of Passive Membrane Permeation from Multiscale Modeling. J Am Chem Soc. 2017 Jan 11;139(1):442-452

MDG43A1S3

Simulated
United atoms MD

Production run with G43a1-s3

GROMOS 43a1-s3 force field is a united atom (UA) force field parametrized for a broad range of biomolecular systems.

[1] S.-W. Chiu, S. A. Pandit, H. L. Scott and E. Jakobsson, J. Phys. Chem. B, 2009, 113, 2748–2763.
[2] S. A. Pandit, S.-W. Chiu, E. Jakobsson, A. Grama and H. L. Scott, Langmuir, 2008, 24, 6858–6865.
[3] S. A. Pandit, S.-W. Chiu, E. Jakobsson, A. Grama and H. L. Scott, Biophys. J., 2007, 92, 920–927.
[4] S. A. Pandit, E. Jakobsson and H. L. Scott, Biophys. J., 2004, 87, 3312–3322.

MDG87

Simulated
United atoms MD

The united atom Gromos 87 force field, with corrections for alkanes and water-CH3 interactions.

van Gunsteren, W. F.; Berendsen, H. J. C., Gromos-87 manual;
Biomos BV: Groningen, The Netherlands, 1987.

van Buuren, A. R.; Marrink, S. J.; Berendsen, H. J. C. A
Molecular Dynamics Study of the Decane/Water Interface. J. Phys.
Chem. 1993, 97, 9206−9212.

Mark, A. E.; van Helden, S. P.; Smith, P. E.; Janssen, L. H. M.;
van Gunsteren, W. F. Convergence Properties of Free Energy
Calculations: Alpha-Cyclodextrin Complexes as a Case Study. J. Am.
Chem. Soc. 1994, 116, 6293−6302.

MDSLA99SB

Simulated
Atomistic MD

The Stockholm lipids (slipids) force field is used for lipids and is comined with the AMBER99SB force field for water and the dye.

 

 

J.P.M. Jämbeck, A.P. Lyubartsev, Derivation and systematic validation of a refined
all-atom force field for phosphatidylcholine lipids, J. Phys. Chem. B 116 (2012)
3164–3179.

J. A. Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, K. E. Hauser, C. Simmerling, "ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB", J. Chem. Theory Comput. 11 (2015), 3696−3713

MDSmC36

Simulated
Hybrid

A numerical solution of the time-fractional Smoluchowski model with an imposed concentration imbalance.

MDUAG

Simulated
United atoms MD

United atom lipid topologies are based on standard GROMACS parameters. These include GROMOS87 parameters included with the GROMACS simulation package and topologies from Tieleman that include GROMOS, Berger and OPLS32 parameters.

MDUSA4A9

Simulated
Atomistic MD

Umbrella sampling with AMBER Lipid14 and AMBER ff99SB

Umbrella sampling is an enhanced sampling technique used in computational chemistry to predict energetical landscape by intensive sampling of conformational space. In calculations of permeation through membranes, a set of initial drug positions across the membrane is estimated. For each of those, a simulation is performed, restraining the drug in position with a harmonic potential to sample the conformational space along reaction coordinate. Using Weighted Histogram Analysis Method (WHAM), PMF is recovered and thermodynamic properties of drug membrane permeation are calculated.

AMBER Lipid14 is the latest force field from AMBER Lipid force fields family, allowing membrane simulation without the need of using additional surface tension. This version of the force field was tested on six different lipid membrane types and is compatible with AMBER protein, nucleic acid, carbohydrates and small molecules force field.

AMBER ff99SB is an all atom (AA) force field with reparametrized phi/psi dihedral terms in energy funcion to better represent secondary structure elements of protein backbone.


 

  • V. Hornak et al. Comparison of multiple AMBER force fields and development of improved protein backbone parameters. Proteins., 2006, 65(3), 712-725, DOI: 10.1002/prot.21123

  • C. J. Dickson et al. Lipid14: The Amber Lipid Force Field. JCTC 2014, 10(2), 865-879 DOI:10.1021/ct4010307

 

MDUSBG56

Simulated
United atoms MD

Umbrella sampling with Berger and GROMOS 53A6

Umbrella sampling is an enhanced sampling technique used in computational chemistry to predict energetical landscape by intensive sampling of conformational space. In calculations of permeation through membranes, a set of initial drug positions across the membrane is estimated. For each of those, a simulation is performed, restraining the drug in position with a harmonic potential to sample the conformational space along reaction coordinate. Using Weighted Histogram Analysis Method (WHAM), PMF is recovered and thermodynamic properties of drug membrane permeation are calculated.

Berger force field for lipids is a united atom (UA) force field extensively tested on DPPC membrane model against experimental data such as lipid densities and heat vaporizations. Lennard-Jones parameters of hydrocarbon chains were tuned with quantum chemical calculations on simple alcanes.

GROMOS S53A6 force field is a united atom (UA) force field parametrized for a broad range of biomolecular systems. Parametrization procedure is focused on reproducing free enthalpies of solvation on a variety of compounds.


 

 

  • O. Berger, et al. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure and constant temperature, Biophys. J., 1997,  72(5), 2002-2013, DOI:10.1016/S0006-3495(97)78845-3

  • C. Oostenbrink, et al. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force field parameter sets 53A5 and 53A6. J. Comput. Chem., 2004, 25(13), 1656-76, DOI: 10.1002/jcc.20090

MDUSC36

Simulated
Atomistic MD

Umbrella sampling with CHARMM36

Umbrella sampling is an enhanced sampling technique used in computational chemistry to predict energetical landscape by intensive sampling of conformational space. In calculations of permeation through membranes, a set of initial drug positions across the membrane is estimated. For each of those, a simulation is performed, restraining the drug in position with a harmonic potential to sample conformational space along the reaction coordinate. Using Weighted Histogram Analysis Method (WHAM), PMF is recovered and thermodynamic properties of drug membrane permeation are calculated.

CHARMM36 is an all atom (AA) force field for lipid simulation with redefined parameters for lipid headgroups (choline and ethanolamine) and both saturated and unsaturated lipid chains based on quantum mechanical and experimental data. Newly derived parameters were tested on fully hydrated bilayers. Parameters for sphingolipids were added.

  • J. B. Klauda et al. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J. Phys. Chem. B. 2010, 114, 7830-7843 DOI: 10.1021/jp101759q

  • R. M. Venable et al. CHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature. Biophys. J. 2014, 107(1), 134-45, DOI: 10.1016/j.bpj.2014.05.034

 

MDUSG43A1S3

Simulated
United atoms MD

Umbrella sampling with GROMOS 43A1-S3

Umbrella sampling is an enhanced sampling technique used in computational chemistry to predict energetical landscape by intensive sampling of conformational space. In calculations of permeation through membranes, a set of initial drug positions across the membrane is estimated. For each of those, a simulation is performed, restraining the drug in position with a harmonic potential to sample the conformational space along reaction coordinate. Using Weighted Histogram Analysis Method (WHAM), PMF is recovered and thermodynamic properties of drug membrane permeation are calculated.

GROMOS 43a1-s3 force field is a united atom (UA) force field parametrized for a broad range of biomolecular systems.

MDUSSlip

Simulated
Atomistic MD

Umbrella sampling with Slipids force fields

Umbrella sampling is an enhanced sampling technique used in computational chemistry to predict energetical landscape by intensive sampling of conformational space. In calculations of permeation through membranes, a set of initial drug positions across the membrane is estimated. For each of those, a simulation is performed, restraining the drug in position with a harmonic potential to sample the conformational space along reaction coordinate. Using Weighted Histogram Analysis Method (WHAM), PMF is recovered and thermodynamic properties of drug membrane permeation are calculated.

Slipids (Stockhol lipids) is was systematicaly derived from CHARMM36 force field and provides improvements in geometry and energies of lipids. FF was parametrized on DMPC lipid bilayer model. 

Jämbeck, J. P. M.; Lyubartsev, P. Derivation and systematic validation of a refined all-atom force field for phosphatidylcholine lipids. J. Phys. Chem. B, 2012, 116, 3164–3179.

Jämbeck, J. P. M.; Lyubartsev, P. Another Piece of the Membrane Puzzle: Extending Slipids Further. J. Chem. Theory Comput. 2012, 9, 774–784.

Jämbeck, J. P. M.; Lyubartsev, P. An Extension and Further Validation of an All- Atomistic Force Field for Biological Membranes. J. Chem. Theory Comput. 2012, 8, 2938–2948.

MMAR

Simulated
Coarse grain MD

Martini force field is a coarse grain molecular dynamics force field with typical 4 heavy atoms : 1 beads mapping scheme. 

 

  • Marrink, S. J.; de Vries, A. H.; Mark, A. E. Coarse grained model for semiquantitative lipid simulations. J. Phys. Chem. B 2004, 108, 750−760.
  • Marrink, S. J.; Risselada, H. J.; Yefimov, S.; Tieleman, D. P.; de Vries, A. H. The MARTINI force field: coarse grained model for biomolecular simulations. J. Phys. Chem. B 2007, 111, 7812−7824.
  • Marrink, S. J.; Tieleman, D. P. Perspective on the Martini model. Chem. Soc. Rev. 2013, 42, 6801−6822.
  • De Jong, D. H.; Baoukina, S.; Ingólfsson, H. I.; Marrink, S. J. Martini straight: Boosting performance using a shorter cutoff and GPUs. Comput. Phys. Commun. 2016, 199, 1−7.

QSAR-HB

Computed
QSAR

QSAR model for prediction of Human intestinal absorption (HIA) and permeability based H-bond donor/acceptor capacieties, Jurs term and Ghose-Crippen octanol-water partition coefficients. Validated on experimental CACO2 permeabilities.

Subramanian G, Kitchen DB.: Computational approaches for modeling human intestinal absorption and permeability. J Mol Model, Volume 12 (5), 577-589, 2006

QSAR-PSA

Computed
QSAR

QSAR model for prediction of Human intestinal absorption (HIA) and permeability based on polar wan der Waals surface area (PSA) and MW. Validated on experimental CACO2 permeabilities. 

 

Subramanian G, Kitchen DB.: Computational approaches for modeling human intestinal absorption and permeability. J Mol Model, Volume 12 (5), 577-589, 2006

XLOGP3

Computed
QSAR

XLOGP3 is a QSAR model for calculation of the logarithmic value of partition coefficient for octanol/water mixture. XLOGP3 has implemented an optimized atom typing scheme and is calibrated on a much larger training set. More importantly, based on the assumption that compounds with similar structures have similar properties, XLOGP3 introduces a new strategy by predicting logP value of a query compound based on the known logP value of a structural analog. 
It is widely used as a benchmark calculation of logP in PubChem. 

  • Tiejun Cheng, Yuan Zhao, Xun Li, Fu Lin, Yong Xu, Xinglong Zhang, Yan Li and Renxiao Wang*, Computation of Octanol-Water Partition Coefficients by Guiding an Additive Model with Knowledge. J. Chem. Inf. Model. 2007, 47
  • http://www.sioc-ccbg.ac.cn/skins/ccbgwebsite/software/xlogp3/manual/XLOGP3_Manual.pdf