2.13.3. Descriptor Definitions

Good descriptors make good models. Most of the ones we use are standard in the chemometrics and modeling literature: detailed descriptions can be found in Todeschini and Consonni's comprehensive Handbook of Molecular Descriptors. Most models only make use of molecular descriptors that are functions of the overall molecular structure (e.g., bond and ring counts or connectivity indices) or simple functions of atomic descriptor vectors for their constituent atoms (sums, averages, maxima, minima, correlation vector elements, etc.). S+pKa, the various CYP site of metabolism models and most CYP kinetics models are exceptions in that they do rely on atomic descriptors.

Atomic descriptors include attributes like elemental type, hybridization state, and hydrogen bond donor or acceptor status, but they also include some specific environmental indicator such as topological proximity to acidic or basic groups. Two sets of descriptors developed by Hall and Kier (1991; 1995) have found particularly wide application. One is the intrinsic state I calculated from a base electronegativity and the atom's molecular connectivity. The other is its electrotopological index (E-State) S, which is its intrinsic state perturbed incrementally by the intrinsic states of atoms to which it is connected, down-weighted by the topological distance to each.

Note that the E-state for an an atom type not found in a molecule is set to 0.

In addition to these standard atomic descriptors, we use an advanced set of proprietary atomic charge and reactivity descriptors derived from an analysis of ~1000 diverse multifunctional molecules, 80% of which were used to train our partial atomic charge models and 20% of which served as a test set. GAMESS calculations were run at the B3LYP/6-311G(d,p) level followed by natural population analysis (NPA) to extract atomic atomic charges. A special protocol using natural bond orbitals (NBO) was employed to extract separate sigma and pi components of the partial atomic charges.

The sigma charges were provided as inputs to parameterize a 2D variant (i.e., one based on topological distances) of the electronegativity equalization method (EEM) based on the formalism of Chaves et al (2006) for the EEM kernel. EEM electronegativity and hardness parameters were fit to the ca. 4000 atoms in our training set using 25 hardness and 49 electronegativity parameters using our extension of Chaves's model. To deal with resonance effects in pi systems, a Hückel Model treatment for pi charges was also developed with additional parameters for pi electronegativity, bond resonance and hyperconjugation.

The final model yielded an RMSE 0.048 for sigma charges and 0.040 for pi charges (in atomic units) on the test set. The overall partial atomic charge RMSE is 0.049.

EEM sigma and Hückel pi Fukui indices - derivatives of atomic partial charge with respect to overall electron count - serve as additional atomic descriptors. They represent measures of reactivity in the sigma and pi systems. The pi Fukui indices come in positive and negative "flavors"; f(+) indices relate to pi electron density for the lowest unoccupied molecular orbital (LUMO), whereas f(-) indices relate to pi electron density in the HOMO (Chattaraj 2006; Anderson 2007).

Inclusion of the new EEM-Hückel model charges and Fukui indices improved the performance of most models examined, typically reducing the test set RMSE (or false rate for classification models) by 10-20%.

Molecular descriptors

ADMET Predictor generates 396 molecular descriptors from 2D structures and an additional 50 from 3D structures. Some of these descriptors are used in the mathematical models for the predicted ADMET properties. A few descriptors are provided for free, but access to the full complement is contingent upon having purchased a license for ADMET Modeler or for one of the four ADMET Properties modules. The complete list of descriptors is presented below, along with a brief explanation of each descriptor.

The descriptors are grouped as they are within the Attribute quick selection dialog (1). That dialog is launched by clicking on any of the quick select ions found on the Arrange spreadsheet columns dialog (as well as on many others in ADMET Predictor), which is itself can be launched from the keyboard (Ctrl+Alt+V) or from the menu bar: VIEW >> Arrange Columns...

Textual Description descriptors are non-numeric and cannot be used for modeling. Indicators are not intended for modeling; their main purpose is to provide you with notice that the corresponding molecular structure cannot be parsed properly by ADMET Predictor. This may be because it contains metals or other elements not generally encountered in pharmacological chemistry or because it contains problematic atom types.

Constitutional descriptors capture various aspects of molecular size and uniformity of composition, whereas Topological Indices summarize molecular shape. Besides such classical connectivity indices as the Kappa Kier-Hall shape descriptors and the Wiener Index, this group includes topological analogs of 3D shape descriptors. The way T_Radmax is calculated, for example, parallels the way RadMax_3D is calculated. The difference is that the former is applied to the topological distance (bond separation) matrix and the latter is applied to the Euclidean distance matrix. Version 13 of the program introduced descriptors of enantiomeric chirality for the first time (Chirxxx). These will be zero for input structures without chiral indicators (e.g., @ and @@ in SMILES).

Electrotopological State descriptors were devised by Kier and Hall and have been widely used in QSAR applications (see Roy 2012 for a review). Descriptors in the Charge-based group are aggregate functions of the atomic descriptors described above. Ionization descriptors, on the other hand, are derived from our S+pKa microstate analysis. These three descriptors groups are particularly important to many of the models that we develop and distribute.

Textual Description:

Formula	Molecular Formula
AcidAtoms	Numeric labels and types of all detected acidic atoms
BaseAtoms	Numeric labels and types of all detected basic atoms
Isoel_pH	Isoelectric pH, well defined only for zwitterionic/ampholytic compounds. It returns "None" for strict acids, strict bases, neutral compounds.

Indicators (not generally appropriate for model building):

N_Nonorgn	Number of atoms other than C, N, O, S, P and halogens.*
N_Metal	Number of metallic element atoms*
N_CYPAtoms	Number of atoms that can potentially be oxidized by CYPs (excludes epoxidation)
N_CYPSites	Number of atoms/bonds that can potentially be oxidized by CYPs (includes epoxidation routes)
N_UGTSites	Number of points of attack by human UGTs
N_AOXSites	Number of atoms that can potentially be oxidized by Aldehyde Oxidase enzyme
N_Kekule	Number of Kekule structures per molecule
S_unknown	The number of unrecognized E-state atom types.*
Unknown_	Number of detected but unassigned functional groups.*

*ADMET Predictor can only properly handle compounds for which N_Nonorgn, N_Metal, S_unknown and Unknown_ are all 0. Compounds for which this is not the case are apt to cause problems in model building and evaluation. Their molecular structures should be checked manually for errors before proceeding. They should probably be set aside, since predictions made for them may not be reliable.

Simple Constitutional Descriptors:

MWt	Molecular Weight (g/mol)
MolVol	Liquid molal volume (cm³/mol) at the normal boiling point; based on Schroeder's method
VMcGowan	Mc Gowan's characteristic volume
N_Atoms	Number of atoms
N_Carbon	Number of carbons
N_Hydrgn	Number of hydrogens
N_Ntrgen	Number of nitrogens
N_Oxygen	Number of oxygens
N_Phsphr	Number of phosphorus atoms
N_Sulfur	Number of sulfurs
N_Boron	Number of borons
N_Fluorn	Number of fluorines
N_Chlorn	Number of chlorines
N_Bromin	Number of bromines
N_Iodine	Number of iodines
N_Halogen	Number of halogen atoms
F_sp3_C	Fraction of carbon atoms with sp³ hybridization
N_Nonorgn	Number of "non-organic" atoms (i.e., atoms other than C,N,O,S,P,halogens)
N_Metal	Number of metallic element atoms
N_Bonds	Number of bonds
N_FrRotB	Number of freely rotatable bonds, terminal bonds excluded. At least one bonded atom must be sp3-hybridized.
F_SgleB	Single bonds as fraction of total bonds.
F_DbleB	Double bonds as fraction of total bonds.
F_TpleB	Triple bonds as fraction of total bonds.
F_AromB	Aromatic bonds as fraction of total bonds.
F_AFRBWF	Average value of the freely rotatable bond weight factor. The FRBW factor is defined as the minimal atom count fraction per bond.
N_Rings	Number of rings
N_AromR	Number of aromatic rings
N_AliphR	Number of aliphatic rings
N_AntiArom	Number of Anti-aromatic rings (rings containing all sp² hybridized atoms with 4N pi electrons and number of pi electrons >= number of ring atoms)
N_Pisyms	Number of distinct π systems, excluding lone pairs
N_PiSysAtoms	Total number of atoms involved in pi systems
N_IsolLP	Number of isolated lone electron pairs
Herndon	Herndon resonance energy

Topological Indices:

X0	Zeroth Order Simple Connectivity Index
X1	First Order Simple Connectivity Index
X2	Second Order Simple Connectivity Index
Kappa1	First Order Simple Kier-Hall shape descriptor
Kappa2	Second Order Simple Kier-Hall shape descriptor
Kappa3	Third Order Simple Kier-Hall shape descriptor
T_Rgrav	Topological equivalent of RgGrav_3D
T_Rgeom	Topological equivalent of RgGeom_3D
T_Radmax	Topological equivalent of RadMax_3D
T_Rada	Topological equivalent of Rada__3D
T_Radb	Topological equivalent of Radb__3D
T_Radc	Topological equivalent of Radc__3D
T_Rads	Topological equivalent of Rads__3D
T_HydroR	Topological equivalent of HydroR__3D
T_MIRxx	Topological equivalent of MIRxx___3D, but without mass weighting
T_MIRyy	Topological equivalent of MIRyy___3D, but without mass weighting
T_Dipole	Topological equivalent of Dipole__3D
T_Lipole	Topological equivalent of Lipole__3D
T_Grav3	Topological equivalent of Grav3__3D
T_RDmtr	Relative topological diameter: maximal topological distance divided by the number of atoms
T_PSA	Topological polar surface area, as defined by P. Ertl, et al.
Wiener	Classical Wiener index of the hydrogen-suppressed molecular graph
Blbn_J	Balaban distance connectivity index J of the hydrogen-suppressed molecular graph
Blbn_MSD	Balaban mean square distance index of the hydrogen-suppressed molecular graph
ddRepul	Number of dipole-dipole repulsions between adjacent or nearby NH groups in ring systems
lpRepul	Number of lone-pair/lone-pair repulsions between adjacent or nearby N or O atoms in ring systems
Zagreb1	Zagreb index of the 1st kind
mZagreb	Modified Zagreb index of the 1st kind
nSPS	Normalized spacial score (molecule complexity)
ChirVol	Descriptor of chirality dependent upon atomic McGowan volumes in individual chiral branches
ChirVolP	Descriptor of chirality dependent upon atomic McGowan volumes in individual chiral branches, scaled by square of distance from chiral center
ChirVolM	Descriptor of chirality dependent upon atomic McGowan volumes in individual chiral branches, scaled by inverse square of distance from chiral center
ChirChg	Descriptor of chirality dependent upon partial atomic charges in individual chiral branches
ChirChgP	Descriptor of chirality dependent upon partial atomic charges in individual chiral branches, scaled by square of distance from chiral center
ChirChgM	Descriptor of chirality dependent upon partial atomic charges in individual chiral branches, scaled by inverse square of distance from chiral center
ChirACh	Descriptor of chirality dependent upon absolute partial atomic charges in individual chiral branches
ChirAChP	Descriptor of chirality dependent upon absolute partial atomic charges in individual chiral branches, scaled by square of distance from chiral center
ChirAChM	Descriptor of chirality dependent upon absolute partial atomic charges in individual chiral branches, scaled by inverse square of distance from chiral center
ChirPol	Descriptor of chirality dependent upon atomic Glen polarizability in individual chiral branches
ChirPolP	Descriptor of chirality dependent upon atomic Glen polarizability in individual chiral branches, scaled by square of distance from chiral center
ChirPolM	Descriptor of chirality dependent upon atomic Glen polarizability in individual chiral branches, scaled by inverse square of distance from chiral center
ChirHBA	Descriptor of chirality dependent upon HB acceptor basicities in individual chiral branches
ChirHBAP	Descriptor of chirality dependent upon HB acceptor basicities in individual chiral branches, scaled by square of distance from chiral center
ChirHBAM	Descriptor of chirality dependent upon HB acceptor basicities in individual chiral branches, scaled by inverse square of distance from chiral center
ChirHBD	Descriptor of chirality dependent upon HB donor acidities in individual chiral branches
ChirHBDP	Descriptor of chirality dependent upon HB donor acidities in individual chiral branches, scaled by square of distance from chiral center
ChirHBDM	Descriptor of chirality dependent upon HB donor acidities in individual chiral branches, scaled by inverse square of distance from chiral center
ChirFlx	Descriptor of chirality dependent upon bond flexibilities in individual chiral branches
ChirFlxP	Descriptor of chirality dependent upon bond flexibilities in individual chiral branches, scaled by square of distance from chiral center
ChirFlxM	Descriptor of chirality dependent upon bond flexibilities in individual chiral branches, scaled by inverse square of distance from chiral center
BCUT_MW_HI	Highest eigenvalue of Burden matrix weighted by atomic weights
BCUT_MW_LO	Lowest eigenvalue of Burden matrix weighted by atomic weights
BCUT_LP_HI	Highest eigenvalue of Burden matrix weighted by atomic lipophilicities
BCUT_LP_LO	Lowest eigenvalue of Burden matrix weighted by atomic lipophilicities
lnHosoyaZ	Logarithm of the sum of the absolute values of the coefficients of the characteristic polynomial of the molecular graph divided by the number of atoms
InfCntnt	Average information content of the molecular graph

Atom-type Electropological State Indices

SsCH3	Atom-type E-state index for -CH3 groups
SdCH2	Atom-type E-state index for =CH2 groups
SssCH2	Atom-type E-state index for -CH2- groups
StCH	Atom-type E-state index for #CH groups
SdsCH	Atom-type E-state index for =CH- groups
SaaCH	Atom-type E-state index for aCHa groups
SsssCH	Atom-type E-state index for >CH- groups
SddC	Atom-type E-state index for =C= groups
StsC	Atom-type E-state index for #C- groups
SdssC	Atom-type E-state index for =C< groups
SaasC	Atom-type E-state index for -Caa groups
SaadC	Atom-type E-state index for =Caa groups (e.g., C=O in theophylline)
SaaaC	Atom-type E-state index for aCaa groups
SssssC	Atom-type E-state index for >C< groups
SsNH2	Atom-type E-state index for -NH2 groups
SdNH	Atom-type E-state index for =NH groups
SssNH	Atom-type E-state index for -NH- groups
SaaNH	Atom-type E-state index for aNHa groups
StN	Atom-type E-state index for #N groups
SdsN	Atom-type E-state index for =N- groups
SdssN	Atom-type E-state index for =N< groups (secondary N-oxide)
SdsssN	Atom-type E-state index for =N<- groups (tertiary N-oxide)
StsN	Atom-type E-state index for -N+# groups (diazonium)
StdN	Atom-type E-state index for #N= groups (azide)
SaaN	Atom-type E-state index for aNa groups
SsssN	Atom-type E-state index for >N- groups
SddsN	Atom-type E-state index for -N== groups (nitro)
SaasN	Atom-type E-state index for aaN- groups (e.g., substituted imidazole)
SaadN	Atom-type E-state index for aaN= groups (aromatic N-oxide)
SaaaN	Atom-type E-state index for aaNa groups (N-fused rings)
SssssN	Atom-type E-state index for >N+< groups (onium)
SsOH	Atom-type E-state index for -OH groups
SdO	Atom-type E-state index for =O groups
SssO	Atom-type E-state index for -O- groups
SsO-	Atom-type E-state index for coordinated O- groups
SaaO	Atom-type E-state index for aOa groups
SsPH2	Atom-type E-state index for -PH2 groups
SssPH	Atom-type E-state index for -PH- groups
SdssPH	Atom-type E-state index for =PH< groups (phosphinate)
SsssP	Atom-type E-state index for >P- groups
SdsssP	Atom-type E-state index for ->P= groups
SssssP	Atom-type E-state index for >P+< groups (phosphonium)
SsssssP	Atom-type E-state index for ->P< groups
SsSH	Atom-type E-state index for -SH groups
SdS	Atom-type E-state index for =S groups
SssS	Atom-type E-state index for -S- groups
SsssS	Atom-type E-state index for -S+< groups (sulfonium)
SaaS	Atom-type E-state index for aSa groups
SdssS	Atom-type E-state index for >S= groups (sulfone)
SddssS	Atom-type E-state index for >S== groups (sulfate)
SssssssS	Atom-type E-state index for ->S<- groups
SsssB	Atom-type E-state index for -B< groups
SaasB	Atom-type E-state index for aaB- groups
SsF	Atom-type E-state index for -F groups
SsCl	Atom-type E-state index for -Cl groups
SsBr	Atom-type E-state index for -Br groups
SsI	Atom-type E-state index for -I groups
SHsOH	Atom-type hydrogen E-state index for -OH groups
SHdNH	Atom-type hydrogen E-state index for =NH groups
SHsSH	Atom-type hydrogen E-state index for -SH groups
SHsNH2	Atom-type hydrogen E-state index for -NH2 groups
SHssNH	Atom-type hydrogen E-state index for -NH- groups
SHtCH	Atom-type hydrogen E-state index for #CH groups
SHCH_321	Atom-type hydrogen E-state index for -CH3, -CH2- and >CH- groups (saturated aliphatic carbon)
SHdCH2	Atom-type hydrogen E-state index for =CH2 groups
SHdsCH	Atom-type hydrogen E-state index for =CH- groups
SHaaCH	Atom-type hydrogen E-state index for aCHa groups (aromatic carbons)

**Charge-based Descriptors*:**

FormalQ	Formal electric charge
ABSQ	Sum of Absolute Values of PEOE Partial Atomic Charges
ABSQon	As above, but only on O and N atoms
MaxQ	Maximal PEOE Partial Atomic Charge
MinQ	Minimal PEOE Partial Atomic Charge
NPA_ABSQ	Sum of absolute values of estimated NPA partial atomic charges
NPA_AQon	As above, but only on O and N atoms
NPA_AQh	As above, but only on H atoms
NPA_AQc	As above, but only on C atoms
NPA_MaxQ	Maximal Estimated NPA Partial Atomic Charge
NPA_MinQ	Minimal Estimated NPA Partial Atomic Charge
NPA_Q1	First component of the autocorrelation vector of estimated NPA partial atomic charges
NPA_Q2	Second component of the autocorrelation vector of estimated NPA partial atomic charges
NPA_Q3	Third component of the autocorrelation vector of estimated NPA partial atomic charges
NPA_Q4	Fourth component of the autocorrelation vector of estimated NPA partial atomic charges
NPA_Q5	Fifth component of the autocorrelation vector of estimated NPA partial atomic charges
NPA_Q6	Sixth component of the autocorrelation vector of estimated NPA partial atomic charges
EEM_AFon	Sum of absolute values of sigma Fukui indices on N and O
EEM_AFc	Sum of absolute values of sigma Fukui indices on C
EEM_AFpl	Sum of absolute values of sigma Fukui indices on polar atoms
EEM_AFnp	Sum of absolute values of sigma Fukui indices on nonpolar atoms
EEM_MaxF	Maximum sigma Fukui index
EEM_XFon	Maximum sigma Fukui index on N and O
EEM_NFon	Minimum sigma Fukui index on N and O
EEM_XFh	Maximum sigma Fukui index on H
EEM_XFc	Maximum sigma Fukui index on C
EEM_NFc	Minimum sigma Fukui index on C
EEM_XFpl	Maximum sigma Fukui index on polar atoms
EEM_NFpl	Minimum sigma Fukui index on polar atoms
EEM_XFnp	Maximum sigma Fukui index on nonpolar atoms
EEM_NFnp	Minimum sigma Fukui index on nonpolar atoms
EEM_F1	First component of the autocorrelation vector of sigma Fukui indices
EEM_F2	Second component of the autocorrelation vector of sigma Fukui indices
EEM_F3	Third component of the autocorrelation vector of sigma Fukui indices
EEM_F4	Fourth component of the autocorrelation vector of sigma Fukui indices
EEM_F5	Fifth component of the autocorrelation vector of sigma Fukui indices
EEM_F6	Sixth component of the autocorrelation vector of sigma Fukui indices
Pi_ABSQ	Sum of absolute values of Hückel pi atomic charges
Pi_AQo	As above, but only on O atoms
Pi_AQn	As above, but only on N atoms
Pi_AQc	As above, but only on C atoms
Pi_MaxQ	Maximum Hückel pi atomic charge
Pi_MinQ	Minimum Hückel pi atomic charge
Pi_Q1	First component of the autocorrelation vector of Hückel pi atomic charges
Pi_Q2	Second component of the autocorrelation vector of Hückel pi atomic charges
Pi_Q3	Third component of the autocorrelation vector of Hückel pi atomic charges
Pi_Q4	Fourth component of the autocorrelation vector of Hückel pi atomic charges
Pi_Q5	Fifth component of the autocorrelation vector of Hückel pi atomic charges
Pi_Q6	Sixth component of the autocorrelation vector of Hückel pi atomic charges
Pi_AFPlc	Sum of absolute values of pi Fukui(+) indices on carbon
Pi_AFMic	Sum of absolute values of pi Fukui(-) indices on carbon
Pi_MaxFPl	Maximum pi Fukui(+) index
Pi_MaxFMi	Maximum pi Fukui(-) index
Pi_FPl1	First component of the autocorrelation vector of pi Fukui(+) indices
Pi_FPl2	Second component of the autocorrelation vector of pi Fukui(+) indices
Pi_FPl3	Third component of the autocorrelation vector of pi Fukui(+) indices
Pi_FPl4	Fourth component of the autocorrelation vector of pi Fukui(+) indices
Pi_FPl5	Fifth component of the autocorrelation vector of pi Fukui(+) indices
Pi_FPl6	Sixth component of the autocorrelation vector of pi Fukui(+) indices
Pi_FMi1	First component of the autocorrelation vector of pi Fukui(-) indices
Pi_FMi2	Second component of the autocorrelation vector of pi Fukui(-) indices
Pi_FMi3	Third component of the autocorrelation vector of pi Fukui(-) indices
Pi_FMi4	Fourth component of the autocorrelation vector of pi Fukui(-) indices
Pi_FMi5	Fifth component of the autocorrelation vector of pi Fukui(-) indices
Pi_FMi6	Sixth component of the autocorrelation vector of pi Fukui(-) indices
EqualChi	Equalized molecular electronegativity
EqualEta	Equalized molecular hardness
Elephity	Electrophilicity index
N_Electr	Total number of electrons in a molecule
PolarizG	Polarizability in A3 calculated by Glen's method
PolarizM	Polarizability in A3 calculated by Miller's method

** *** The charge unit is the absolute charge on an electron.

Hydrogen Bonding Descriptors:

IHB	Number of Intra-molecular Hydrogen Bonds
PHB	Proximity Effects of HB Donors and HB Acceptors. Similar to IHB, but counts all possible donor-acceptor pairs within the IHB range.
HBD	Number of OH and NH Hydrogen Bond Donors
HBDH	Number of OH and NH Hydrogen Bond Donor Protons
HBA	Number of O and N Hydrogen Bond Acceptors
HBDo	Number of Oxygen-based Hydrogen Bond Donors
HBAo	Number of Oxygen-based Hydrogen Bond Acceptors
HBDn	Number of Nitrogen-based Hydrogen Bond Donors
HBAn	Number of Nitrogen-based Hydrogen Bond Acceptors
HBDch	Sum of Estimated NPA Partial Atomic Charges on HB Donor Hydrogens
HBAch	Sum of Estimated NPA Partial Atomic Charges on HB Acceptors
HBDoch	Sum of Estimated NPA Partial Atomic Charges on Oxygen-based HB Donor Hydrogens
HBAoch	Sum of Estimated NPA Partial Atomic Charges on Oxygen-based HB Acceptors
HBDnch	Sum of Estimated NPA Partial Atomic Charges on Nitrogen-based HB Donor Hydrogens
HBAnch	Sum of Estimated NPA Partial Atomic Charges on Nitrogen-based HB Acceptors
lrIHB	Number of long-range (>3 bonds away) intramolecular hydrogen donor-acceptor pairs
avgIHBdist	Average topological distance between long-range intramolecular hydrogen donor-acceptor pairs
avgIHBstrn	Average strength of interaction (HBacidity*HBbasicity) between long-range intramolecular hydrogen donor-acceptor pairs
maxIHBstrn	Maximum strength of interaction (HBacidity*HBbasicity/100) between long-range intramolecular hydrogen donor-acceptor pairs
distIHBmax	Topological distance between strongest long-range intramolecular hydrogen donor-acceptor pair
avgHBAperD	Average number of long-range intramolecular hydrogen acceptors per donor
avgHBDperA	Average number of long-range intramolecular hydrogen donors per acceptor

Molecular Ionization Descriptors:

N_IoAcAt	Number of recognized ionizable atom types that are acidic
N_IoBaAt	Number of recognized ionizable atom types that are basic
FAnion	Cumulative Contribution of Purely Anionic Species to Fraction Ionized at Specified pH (default = 7.4)
FCation	Cumulative Contribution of Purely Cationic Species to Fraction Ionized at Specified pH (default = 7.4)
FUnion	Cumulative Contribution of All Species with Zero Formal Charge to Fraction Ionized at Specified pH (default = 7.4)
FZwitter	Portion of FUnion Contributed by Zwitterionic Species independent of pH
QAvgNeg	Absolute Value of the Population Average Across All Ionized Species of the Net Formal Negative Charge Calculated at Specified pH (default = 7.4)
QAvgPos	Population Average Across All Ionized Species of the Net Formal Positive Charge Calculated at Specified pH (default = 7.4)
F_NLP	Population Average Across All Ionized Species of the Number of Lone Electron Pairs on N,O,S,P, Divided by the Number of Atoms
F_HBP	Population Average Across All Ionized Species of the Number of Protons Available for Hydrogen Bonding, Divided by the Number of Atoms

Functional Groups:

AlHdrxl_-OH	Number of aliphatic hydroxyl groups
ArHdrxl_-OH	Number of aromatic hydroxyl groups
Carbonyl_C=O	Number of carbonyl (ketone or aldehyde) groups
Ether___-O-	Number of ether groups
PriAmine_-NH2	Number of primary amines
PriAmAli_-NH2	Number of primary amines attached to aliphatic carbon
PriAmAro_-NH2	Number of primary amines attached to aromatic carbon
SecAmine_>NH	Number of primary and aliphatic N secondary amines
TerAmine_>N-	Number of tertiary amine groups
QuaAmine_>[N+]<	Number of quaternary amine groups
ArNitrog_=N-	Number of aromatic nitrogens
Imine___=N-	Number of Imine groups
Nitrile_C#N	Number of Nitrile groups
Isocynd_[N+]#[C-]	Number of Isocyanide groups
Thiol___-SH	Number of Thiol groups
ThioCrbl_C=S	Number of Thiocarbonyl groups
Sulfide_-S-	Number of Sulfide groups
Slfonium_>[S+]-	Number of Sulfonium groups
Phsphine_>P-	Number of Phosphine groups
HydxlAmn_>N-O-	Number of Hydroxyamine groups
Oxime___=N-O-	Number of Oxime groups
Nitroso_-N=O	Number of Nitroso groups
N-oxide_>[N+][O-]	Number of N-oxide groups
Hdrzine_>N-N<	Number of Hydrazine groups
Hdrzone_=N-N<	Number of Hydrazone groups
Azo_____-N=N-	Number of Azo groups
Diazo___-[N+]#N	Number of Diazo groups
ThioAmin_>N-S-	Number of Thioamine groups
Disulfde_-S-S-	Number of Disulfide groups
Sulfoxde_>S=O	Number of Sulfoxide groups
Thioxime_=N-S-	Number of Thioxime groups
Nitro___-NO2	Number of Nitro groups
Nitrite_-O-N=O	Number of Nitrite groups
Ntrosam_>N-N=O	Number of Nitrosamine groups
Azoxy___-N(=O)=N-	Number of Azoxy groups
Azide___-N=N#N	Number of Azide groups
Sulfone_>S(=O)=O	Number of Sulfone groups
Sulfinat_S(=O)O-	Number of Sulfinate groups
Phsporat_P(=O)O-	Number of Phosphorate groups
Triazo__-N-N-N-	Number of Triazo groups
Oxadiazo_-N-O-N-	Number of Oxadiazo groups
Thiadiaz_-N-S-N-	Number of Thiadiazo groups
Triazene_-N=N-N-	Number of Triazene groups
Nitrate_-O-NO2	Number of Nitrate groups
NNitro__>N-NO2	Number of N-connected nitro groups
Sulfonat_-SO3-	Number of Sulfonate groups
Sulfite_-SO3<	Number of Sulfite groups
Sulfonmd_-SO2-N<	Number of Sulfonamide groups
PriSlfmd_-SO2-NH2	Number of Primary Sulfonamide groups
Phsponat_-PO3<	Number of Phosphonate groups
Sphspnat_-SPO2<	Number of Thiolophosphonate groups
Phspite_-OPO2<	Number of Phosphite groups
Tetrazo_-NNNN-	Number of Tetrazo groups
Oxdzoxde_-N(=O)ON-	Number of Oxadiazooxide groups
NOHydxam_ -N(N=O)OH	Number of N-nitrosohydroxylamine groups
Sulfamid_>NSO2N<	Number of Sulfamide groups
Sulfate_-OSO3	Number of Sulfate groups
ThioSulf_-SSO3	Number of Thiosulfate groups
Phspate_O=PO3<-	Number of Phosphate groups
PhspatS_ O=PS(k)O(3-k)<-	Number of ThioloPhosphate groups: O=P(X)(X)X where X = S,O
Sphspat_S=PO3<-	Number of ThioPhosphate groups
SphspatS_ S=PS(k)O(3-k)<-	Number of ThioThioloPhosphate groups: S=P(X)(X)X where X = S,O
PhspatN_ O=PN(n)O(3-n)<<<	Number of Phosphamide groups: O=P(X)(X)X where X = N,O
SphspatN_ S=PN(n)O(3-n)<<<	Number of ThioPhosphamide groups: S=P(X)(X)X where X = N,O
PhsptSN_ O=PS(k)N(n)O(3-n-k)<<	Number of ThioloPhosphamide groups: O=P(X)(X)X where (X = N,O,S)
SPhsptSN_ S=PS(k)N(n)O(3-n-k)<<	Number of ThioThioloPhosphamide groups: S=P(X)(X)X where (X = N,O,S)
Diphspat_ O=PO2-O-PO2=O	Number of Diphosphate groups
Triphspt_ O=PO2-O-PO(=O)-OPO2=O	Number of Triphosphate groups
AlCbxyl_-COOH	Number of Aliphatic Carboxyl groups
ArCbxyl_-COOH	Number of Aromatic Carboxyl groups
Ester___C(=O)OC	Number of Ester groups
Amide___C(=O)N<	Number of Amide groups
Thioamd_C(=S)N<	Number of Thioamide groups
Amidine_C(=N-)N<	Number of Amidine groups
Isocyant_-N=C=O	Number of Isocyanate groups
Thiocynt_-S-C#N	Number of Thiocyanate groups
Isothcnt_-N=C=S	Number of Isothiocyanate groups
Urea____>NC(=O)N<	Number of Urea groups
Carbmte_>NC(=O)O-	Number of Carbamate groups
Guandne_>NC(=N-)N<	Number of Guanidine groups
Imide___O=C(N-)C=O	Number of Imide groups
Barbitur_ C1C(=O)NC(=O)NC1=O	Number of Barbiturate groups
AromAmide_c(=O)[nH]	Number of aromatic amide bonds (e.g. as in 2-pyridone)

Moriguchi Descriptors used in calculating MlogP:

Parameter	Description	Example
M_CX	Summation of numbers of carbon and halogen atoms weighted by C:1.0, F:0.5, Cl:1.0, Br:1.5, and I:2.0.
M_NO	Total number of N and O atoms
M_PRX	Proximity effect of N & O; where X-Y:2.0, X-A-Y:1.0 (X,Y can be N or O and A can be C,S, or P) with a correction (-1) for carboxamide/sulfonamide.	= 2 = 1
M_UB	Total number of unsaturated bonds except those in NO2	= 3
M_HB	Number of intramolecular hydrogen bonds as ortho –OH and –C(=O)-R, or –OH and –NH2, or –NH2 and –COOH, or 8-OH/NH2 in quinolines, etc.
M_POL	Number of aromatic polar substituents (aromatic substituents excluding Ar-CX2- and Ar-CX=C<, where X: is C or H.	= 2
M_AMP	Amphoteric property; α-amino acid:1.0, amino benzoic acid: 0.5, pyridinecarboxylic acid 0.5. =0.5 =0.5	= 1.0
M_ALK	Indicator variable for alkane, alkene, cycloalkane, or cycloalkene (hydrocarbons with 0 or 1 double bond)
M_RNG	Indicator variable for the presence of ring structures except benzene and its condensed rings (aromatic, heteroaromatic, and hydrocarbon rings)- e.g., excluding:
M_QN	Quaternary nitrogen: >N+<: 1.0, N oxide:0.5 =0.5
M_NO2	Number of nitro groups
M_NCS	Isothiocyanate (-N=C=S): 1.0, thiocyanate (-S-C#N): 0.5
M_BLM	Indicator variable for the presence of β-lactam.

Pattern Recognition Flags:

AlphaAA	Alpha Amino Acid Flag
PrAlphAA	Primary Alpha Amino Acid Flag
AlphaAE	Alpha Amino Ester Flag
PrAlphAE	Primary Alpha Amino Ester Flag
Steroid	Flag Indicating Steroid-like Fused Ring Subunit
N_Thiophenes	Number of thiophene rings
N_Thiazoles	Number of thiazole rings
N_Furans	Number of furan rings
N_Oxazoles	Number of oxazole rings
N_Imidazoles	Number of imidazole rings
N_Piperidines	Number of piperidine rings
N_Piperazines	Number of piperazine rings
N_Pyridines	Number of pyridine rings
N_PhenolOH	Number of -OH groups connected to phenyl rings
N_Ureas	Number of urea moieties (note: this is different from Urea functional groups!)
N_UnbrChains	Number of unbranched chains of sp3 atoms of length >= 4
N_QuaternaryN	Number of aliphatic quaternary amines (QuaAmine_>[N+]< also counts aromatic q.a.)
N_Sulfide	Number of aliphatic sulfides (Sulfide_-S- also counts aromatic sulfides)
N_PrimAmides	Number of primary amides (note: this is different from Amide functional groups!)
Macrocycle	An indicator of the presence of a large (12 atoms or more) ring

Indicator variables (not counts) specific to Meylan solubility models:

Parameter	Description	Exceptions
H_AlAlco (Aliphatic Alcohol)	Compounds with exactly one OH group attached to an aliphatic hydrocarbon	Compounds with any functional group, including a second OH group
H_AlAcid (Aliphatic Acid)	Compounds with one or more carboxylate groups attached to aliphatic carbons	Amino acids (aliphatic or aromatic amines, except quaternary) and amides
H_AlAmin (Aliphatic Amine)	Compounds with primary, secondary, or tertiary amines attached to aliphatic carbons	Compounds with a melting point greater > 25ºC
H_ArAcid (Aromatic Acid)	Compounds with at least one carboxylate group attached to an aromatic carbon	Compounds with an amino group attached to the same ring to which the carboxylate is attached. “Amino” = aliphatic nitrogen whose only attachments are carbons or other nitrogens.
H_Phenol (Phenol)	Compounds with at least one OH attached to an aromatic carbon	Compounds with an amino group on the same ring and those with nitro, alkyloxy or other OH ortho to OH
H_AlPyri (Alkylpyridine)	Compounds with at least one pyridine ring	Only alkyl substituents allowed; carbon attached to ring must by CH3, CH2-, or CH<
H_Azo (Azo)	Compounds with -N=N-	Both N’s must be attached to carbon
H_Nitrile (Nitrile)	Compounds with -CN	N=C-CN, C=N-CN
H_Hcarb (Hydrocarbon)	Aliphatic compounds with only C and H
H_Nitro (Nitro)	Aliphatic and aromatic compounds with nitro (-NO2) group	N attachment or any amino or OH group if the nitro group is on an aromatic ring
H_SO2 (SO2)	Compounds with at least one sulfonamide on aromatic ring plus an other substituent that is ketone, sulfone, or another sulfonamide on the same ring; also applies to compounds with -S(=O)-C-C(=O)-C (number of Os on S is not limited)
H_Falkan (Fluoroalkane)	Hydrocarbons with at least one fluorine
H_PAH (Polycyclic aromatic hydrocarbon)	Hydrocarbons with at least three rings, at least two of which must be aromatic.
H_MultiN (Multi-N)	Compounds with at least one of the following: - four or more aromatic nitrogens - no aromatic and two or more aliphatic nitrogens. Exactly one aliphatic N must be attached to C(=O), C(=S), or S(=O) - two or more aromatic and two or more aliphatic nitrogens. All aliphatic nitrogens must be attached to C(=O), C(=S), or S(=O)	Compounds with at least one of the following: - sulfonamide - barbiturate - metal atom or ion Excluded from aliphatic nitrogen count are: - nitro - nitrile - azo
H_AmAcid (Amino Acid)	Compound contains at least one carboxylate and at least one amino group.	Compounds with aromatic attachment of at least one carboxylate group.

3D Descriptors (length unit=angstrom, mass unit=dalton):

RgGrav__3D	Gravitational radius of gyration
RgGeom__3D	Geometrical radius of gyration
RadMax__3D	Distance between center of mass and the most distant atom
Propr1__3D	Simulations Plus proprietary descriptor
Rada__3D	Largest ellipsoidal radius of the molecule, based on geometry
Radb__3D	Medium ellipsoidal radius of the molecule, based on geometry
Radc__3D	Smallest ellipsoidal radius of the molecule, based on geometry
Rads__3D	Projected geometrical radius of the molecule, averaged over all orientations
HydroR__3D	Hydrodynamic radius of molecular ellipsoid
MIRxx___3D	Largest relative principal moment of inertia
MIRyy___3D	Medium relative principal moment of inertia
MIRzz___3D	Smallest relative principal moment of inertia
SM2xx___3D	Smallest relative principal static moment of the second order
SM2yy___3D	Medium relative principal static moment of the second order
SM2zz___3D	Largest relative principal static moment of the second order
BoxX____3D	Smallest dimension of the tightest enclosing box in A
BoxY____3D	Medium dimension of the tightest enclosing box in A
BoxZ____3D	Largest dimension of the tightest enclosing box in A
DStokes_3D	Stokes-Einstein diffusion coefficient (cm^2/s x 10^5)
Propr2__3D	Simulations Plus proprietary descriptor
Grav3___3D	Cube root of Wessel gravitational index
TotASA__3D	Total solvent accessible surface area in A^2
PolASA__3D	Polar solvent accessible surface area in A^2
NpoASA__3D	Nonpolar solvent accessible surface area in A^2
SolvE___3D	Aqueous solvation energy in kcal/mol
SolvEMt_3D	Length of the solvation energy moment vector in A*kcal/mol
PEoED___3D	Proximity effects of electron donors. Descriptor derived from Anna Seelig's work on P-glycoprotein substrate recognition patterns.
PEoEDIa_3D	Proximity effects of electron donors of type I including atoms with hydrogens. Descriptor derived from Anna Seelig's work on P-glycoprotein substrate recognition patterns.
PEoEDIb_3D	Proximity effects of electron donors of type I excluding atoms with hydrogens. Descriptor derived from Anna Seelig's work on P-glycoprotein substrate recognition patterns.
PEoEDIIa3D	Proximity effects of electron donors of type II including atoms with hydrogens. Descriptor derived from Anna Seelig's work on P-glycoprotein substrate recognition patterns.
PEoEDIIb3D	Proximity effects of electron donors of type II excluding atoms with hydrogens. Descriptor derived from Anna Seelig's work on P-glycoprotein substrate recognition patterns.
HBAsa___3D	Total solvent accessible surface area on HB acceptors
HBAwsa__3D	Estimated NPA charge-weighted solvent accessible surface area on HB acceptors
PosASA__3D	Positively NPA-charged solvent accessible surface area
NegASA__3D	Negatively NPA-charged solvent accessible surface area
Dipole__3D	Estimated NPA dipole moment
Lipole__3D	3D lipole moment (an estimate of the separation of hydrophobic and hydrophilic regions of a molecule much like dipole moment measures the separation of positive and negative charge).
WHIM_L1s_3D	1st component size directional WHIM index / weighted by relative I-states
WHIM_L2s_3D	2nd component size directional WHIM index / weighted by relative I-states
WHIM_L3s_3D	3rd component size directional WHIM index / weighted by relative I-states
WHIM_E1s_3D	1st component accessibility directional WHIM index / weighted by relative I-states
WHIM_E2s_3D	2nd component accessibility directional WHIM index / weighted by relative I-states
WHIM_E3s_3D	3rd component accessibility directional WHIM index / weighted by relative I-states
WHIM_As_3D	2nd order non-directional WHIM index / weighted by relative I-states
WHIM_Vs_3D	3rd order non-directional WHIM index / weighted by relative I-states
WHIM_Ks_3D	Non-directional WHIM shape index / weighted by relative I-states
Eccentricity_3D	Eccentricity of inertia
InertialSF_3D	Inertial shape factor
MIratio_yx_3D	Ratio of principal moments of inertia yy/xx
MIratio_zx_3D	Ratio of principal moments of inertia zz/xx