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Contributors & References
Some of the definitions also appear in the Glossary of Terms used
in Medicinal Chemistry (IUPAC recommendations 1996; © 1996 IUPAC).
These are marked with an asterisk. For some definitions the more extended
form taken from the Glossary of Terms in Theoretical Organic Chemistry (IUPAC recommendations 199*; © 199*
IUPAC) is included in smaller
font.
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Ab initio calculations
Ab initio calculations are quantum chemical calculations using
exact equations with no approximations which involve the whole electronic
population of the molecule.
Ab initio quantum mechanical methods (Synonymous
with non-empirical quantum mechanical methods) - Methods of quantum mechanical
calculations independent of any experiment other than the determination
of fundamental constants. The methods are based on the use of the full
Schrödinger equation to treat all the electrons of a chemical system.
In practice, approximations are necessary to restrict the complexity of
the electronic wavefunction and to make its calculation possible.
AM1 calculations
AM1 calculations are semi-empirical molecular orbital calculations developed
at the University of Austin in Texas (AM1 = Austin Model 1). These calculations
involve the valence electrons of the atoms of the molecule. They are a
further development of MNDO calculations (Wylie,
1994). (see MNDO calculations)
AMBER
AMBER is a well-known molecular
mechanics program for calculations on proteins and nucleic acids. (see Molecular mechanics)
Artificial
neural networks
Artificial neural networks (ANN) are algorithms simulating the functioning
of human neurons and may be used for pattern recognition problems, e.g.,
to establish quantitative structure-activity relationships.
Atomic orbitals (AO)
Atomic orbitals are mathematical functions (e.g., Gaussian, or Slater functions)
used in quantum chemical calculations. A set of atomic orbitals described
by a defined function is the basis set of atomic orbitals. (see Slater-type
orbitals)
Orbital (Atomic or Molecular) - A wavefunction
which depends explicitly on the spatial coordinates of only one electron.
Basis set
A basis set is a set of mathematical functions used in molecular orbital
(MO) calculations, e.g., the 6-31G* basis set used in ab initio calculations.
6-31G* and similar expression refers to the type of mathematical function
used. (see Molecular orbital (MO) calculations)
Basis set - A set of basis functions employed for
the representation of molecular orbitals. One may distinguish the minimal
basis set (includes one basis function for each SCF (SCF = Self-Consistent
Field) occupied atomic orbital with distinct principal and angular momentum
quantum numbers); split valence basis set (includes two or more sizes of
basis function for each valence orbital); double zeta (DZ) basis set (a
split valence basis set that includes exactly twice as many functions as
the minimal basis set; extended basis set (the set larger than the double
zeta basis set); polarized basis set (incorporates basis functions of higher
angular quantum number beyond what is required by the atom in its electron
ground state; allows orbitals to change not only size, but also shape);
basis set with diffuse functions and others.
Chemometrics
Chemometrics is the application of statistics to the analysis
of chemical data (from organic, analytical or medicinal chemistry) and
design of chemical experiments and simulations.
CLOGP values
CLOGP values are calculated 1-octanol/water partition coefficients, frequently
used in structure-property correlation or quantitative structure-activity
relationship (SPC/QSAR) studies (Leo,
1993) (see Structure-property correlations (SPC) and Quantitative structure-activity relationships (QSAR))
Cluster analysis
Cluster analysis is the clustering, or grouping, of large data sets (e.g.,
chemical and/or pharmacological data sets) on the basis of similarity criteria
for appropriately scaled variables that represent the data of interest.
Similarity criteria (distance based, associative, correlative, probabilistic)
among the several clusters facilitate the recognition of patterns and reveal
otherwise hidden structures (Rouvray,
1990; Willett, 1987, 1991).
CNDO/2 calculations
CNDO/2 calculations are semi-empirical molecular orbital (MO) calculations
using complete neglect of differential overlap. (see
Molecular orbital (MO) calculations)
Comparative molecular field analysis (CoMFA)*
Comparative Molecular Field Analysis (CoMFA) is a 3D-QSAR method that uses
statistical correlation techniques for the analysis of the quantitative
relationship between the biological activity of a set of compounds with
a specified alignment, and their three-dimensional electronic and steric
properties. Other properties, such as hydrophobicity and H-bonding can
also be incorporated into the analysis (Cramer
et al., 1988; Kubinyi, 1993b). (see 3D-QSAR, Hydrophobicity).
Computational chemistry* Computational
chemistry is a discipline using mathematical methods for the calculation
of molecular properties or for the simulation of molecular behaviour. It
also includes, e.g., synthesis planning, database searching, combinatorial
library manipulation (Hopfinger,
1981; Ugi et al., 1990).
Computer-assisted drug design (CADD)*
Computer-assisted drug design involves all computer-assisted techniques
used to discover, design and optimize biologically active compounds with
a putative use as drugs. (see Drug design)
Computer-assisted molecular design (CAMD)
Computer-assisted molecular design involves all computer-assisted techniques
used to discover, design and optimize compounds with desired structure
and properties.
Computer-assisted molecular modeling (CAMM)
Computer-assisted molecular modeling is the investigation of molecular
structures and properties using computational chemistry and graphical visualization
techniques.
Computer chemistry
Computer chemistry is often used as equivalent to computational
chemistry, and can also refer to the use of computers in synthesis planning
(Ugi et al., 1990;
Boyd, 1990).
Conformational analysis
Conformational analysis consists of the exploration of energetically
favorable spatial arrange-ments (shapes) of a molecule (conformations)
using molecular mechanics, molecular dynamics, quantum chemical calculations
or analysis of experimentally-determined structural data, e.g., NMR or
crystal structures. Molecular mechanics and quantum chemical methods are
employed to compute conformational energies, whereas systematic and random
searches, Monte Carlo, molecular dynamics, and distance geometry are methods
(often combined with energy minimization procedures) used to explore the
conformational space. (see Distance geometry, Molecular dynamics, Molecular
Mechanics, Monte Carlo technique, Quantum
chemical methods).
Conformationally flexible searching (CFS)
Conformationally flexible searching is a three dimensional-structure
database search taking into account the flexibility of molecules.
Connolly surface
The Connolly surface is the envelope traced out by the point
of contact of a defined probe (e.g., a sphere) and a molecule of interest
where they touch once, plus the van der Waals surface of the probe where
it touches twice or more (the re-entrant surface), It is used to visualize
the molecular surface.
Craig plot
A Craig plot is a plot of two substituent parameters (e.g.,
Hansch-Fujita p and Hammett s values) used in analog design.
CSSR
The CSSR (Crystal Structure Search Retrieval) file format is
one of several used by the Cambridge Crystal Structure Database (CSD) to
store molecular structures. This format is used in many molecular modeling
software packages.
De novo design*
De novo design is the design of bioactive compounds by the incremental
construction of a ligand model within the receptor or enzyme active site,
the structure of which is known from X-ray or nuclear magnetic resonance (NMR) data.
Discriminant analysis
Discriminant analysis is a statistical technique to find a set
of descriptors which can be used to detect and rationalize separation between
activity classes.
Distance geometry
Distance geometry is a mathematical method used to build three-dimensional
(3D) molecular models from a set of approximate interatomic distances (e.g.,
nuclear Overhauser effect (NOE) experiments in nuclear magnetic resonance (NMR) suggest only ranges of distances). Distance geometry can be used
to define a 3D pharmacophore starting from a set of molecules with the
same mechanism of action, or for the generation of likely geometries for
drug-receptor complexes using intermolecular distance constraints. (Crippen,
1988).
Docking studies
Docking studies are computational techniques for the exploration
of the possible binding modes of a substrate to a given receptor, enzyme
or other binding site.
D-optimal design
D-optimal design is an experimental design technique based on
the optimization of the determinant calculated from the variance-covariance
matrix of the descriptors. It is used to maximize the efficiency of fractional (uncomplete) factorial design. (see Factorial
design, Fractional factorial
design)
3D-QSAR (three-dimensional
quantitative structure-activity relationships)*
Three-dimensional quantitative structure-activity relationships (3D-QSAR)
involves the analysis of the quantitative relationship between the biological
activity of a set of compounds and their three-dimensional properties using
statistical correlation methods.
Drug design
Drug design includes not only ligand design, but also pharmacokinetics
and toxicity, which are mostly beyond the possibilities of structure- and/or
computer-aided design. Nevertheless, appropriate chemometric tools, including
experimental design and multivariate statistics, can be of value in the
planning and evaluation of pharmacokinetic and toxicological experiments
and results. Drug design is most often used instead of the correct term
“Ligand Design”.
Electrostatic field and potential
The electrostatic field and potential are properties of a molecule
arising from the interaction between a charged probe, such as a positive
unit point charge reflecting a proton, and a target molecule. These fields
and potential are being used in three-dimensional quantitative structure-activity
relationship (3D-QSAR) studies and to compare or assess the similarity
of a set of molecules.
Electrostatic potential - A physical property equal
in magnitude to the electrostatic energy between the static charge distribution,
r(r), of an atomic or molecular system and a positive unit point charge
located at r. The electrostatic potential V(r) that is produced at any
point r by the electrons and nuclei (A) of the system is given by i.e. V(r) = S
ZA/|RA-r| - ò r(r’)dr’/|r’-r|.
Energy minimization
Energy minimization is a mathematical procedure to locate the
stable conformations of a molecule (energy minima), as determined by molecular
mechanics or quantum mechanical calculations. (see Molecular mechanics, Quantum chemical calculations).
Experimental design
Experimental design is the use of mathematical and statistical methods
to select the minimum number of experiments or compounds for optimal coverage
of descriptor or variable space.
Extended Hückel (EH) calculations
Extended Hückel calculations are low-level semi-empirical
molecular orbital (MO) calculations.
Extended Hückel method - A semi-empirical
all-valence electron quantum mechanical method which uses the same approximations,
apart from p-approximation and neglect of overlap integrals, as those of
Hückel molecular orbital theory. The method reproduces relatively
well the shapes and the order of energy levels of molecular orbitals. The
account for overlap makes it possible to describe the net destabilization
caused by interaction of two double occupied orbitals.
Extrathermodynamic approach
The extrathermodynamic approach involves the correlation between
variables which, from a strictly thermodynamic standpoint, are not related.
It is the basis of Hansch analysis used in traditional QSAR (Kubinyi,
1993a).
Factorial design
(FD)
Factorial design is an experimental design technique in which
each variable (factor or descriptor) is investigated at fixed levels. In
a two-level FD, each variable can take two values, e.g., high and low
lipophilicity.
File format
The (molecular) file format describes the layout of a computer
data file. It is a set of instructions on how a molecule is encoded with
respect to its connectivity, atom types, coordinates, and may also contain
bibliographic data.
Force field The force field is a
set of functions and parametrization used in molecular mechanics calculations.
Force field - Within the molecular mechanics approach,
a set of potential functions defining bond stretch, bond angle (both valence
and dihedral) distortion energy of a molecule as compared with its nonstrained
conformation (that characterized by standard values of bond lengths and
angles). A set of transferable empirical force constants is preassigned
and the harmonic approximation is usually employed. Some force fields may
contain terms for interactions between non-bonded atoms, electrostatic,
hydrogen bond and other structural effects as well as account for anharmonicity
effects. In vibrational spectroscopy, the inverse problem is solved of
determining a set of force constants and other parameters of a choosen
potential energy functions which would match with experimentally observed
vibrational frequencies of a given series of congeneric molecules.
Fractional
factorial design (FFD)
Fractional factorial design is an experimental design technique,
using a reduction factor in order to limit the number of experiments to
a lower number than obtained by factorial design. Free energy perturbation
calculations Free energy perturbation calculations are mathematical procedures
used in molecular dynamics studies to gradually convert one chemical species
to another in a thermodynamic cycle.
Free-Wilson (FW) analysis
Free-Wilson analysis is a regression technique using the presence
or absence of substituents or groups as the only molecular descriptors
in correlations with biological activity (Kubinyi,
1993a).
Gaussian-type
orbitals (GTO)
Gaussian-type orbitals are mathematical functions used in ab
initio calculations. They have superceded Slater-type orbitals because
of the greater computational efficiency that results. (see Slater-type
orbitals)
Genetic algorithm
A genetic algorithm is an optimization algorithm based on the mechanisms
of Darwinian evolution which uses random mutation, crossover and selection
procedures to breed better models or solutions from an originally random
starting population or sample (Rogers
and Hopfinger, 1994).
GOLPE
Generating optimal linear PLS estimations. It is an advanced variable selection
technique in partial least squares (PLS) used in three-dimensional quantitative
structure-activity relationships (3D QSAR) studies to handle very large
data sets. (see Partial least squares (PLS))
GRID
GRID is a program for receptor/ligand mapping. It calculates
interaction energies between probes and target molecules at interaction
points on a 3D grid (Goodford,
1985).
Hamiltonian
The Hamiltonian is a mathematical operator function used in molecular orbital
calculations (Wylie,
1994).
Hammett constant s
The Hammett constant is an electronic substituent descriptor reflecting
the electron-donating or -accepting properties of a substituent (Hansch
et al., 1995).
Hansch analysis*
Hansch analysis is the investigation of the quantitative relationship between
the biological activity of a series of compounds and their physicochemical
substituent or global parameters representing hydrophobic, electronic,
steric and other effects using multiple regression correlation methodology
(Hansch and Fujita,
1964; Kubinyi, 1993a).
Hansch-Fujita p constant
The Hansch-Fujita p constant describes the contribution of a
substituent to the lipophilicity of a compound (Hansch
and Fujita, 1964).
Highest occupied molecular
orbital (HOMO) energy
The highest occupied molecular orbital (HOMO) energy is obtained
by molecular orbital calculations and relates to the ionization potential
of a molecule and its reactivity as a nucleophile. (see Lowest
unoccupied molecular orbital (LUMO) energy)
Frontier orbital - The molecular orbitals that
involve the highest occupied molecular orbital (HOMO) and the lowest unoccupied
molecular orbital (LUMO) of a given molecular entity. In the case of an
odd-electron molecular entity, when its HOMO is occupied by a single electron
such a molecular orbital is termed a singly occupied molecular orbital (SOMO). Depending on the properties of the reactive partner, the SOMO of
a given species may function as either HOMO or LUMO. The special importance
of the frontier orbitals is due to the fact that a broad variety of chemical
reactions takes place at a position and in a direction where the overlap
of HOMO and LUMO of the respective reactants is maximal.
Homology model
A homology model is a model of a protein, whose three-dimensional structure
is unknown, built from, e.g., the X-ray coordinate data of similar proteins
or using alignment techniques and homology arguments.
Hydrophilicity*
Hydrophilicity is the tendency of a molecule to be solvated by water.
Hydrophobic fragmental constant (f or f’)
The hydrophobic fragmental constant of a substituent or molecular
fragment represents the lipophilicity contribution of that molecular fragment
(Rekker and De Kort,
1979; Hansch and Leo, 1979; Rekker and Mannhold, 1992).
Hydrophobicity*
Hydrophobicity is the association of non-polar groups or molecules in an
aqueous environment which arises from the tendency of water to exclude
non-polar molecules (Martin,
1978; Martin et al., 1989; Dean, 1990).
Indicator variable
An indicator variable is a descriptor that can assume only two values indicating
the presence (=1) or absence (=0) of a given condition. It is often used
to indicate the absence or presence of a substituent or substructure. More
broadly, it is a variable which can encode anything that the investigator
chooses.
Ligand design
Ligand design is the design of ligands using structural information
about the target to which they should bind, often by attempting to maximize
the energy of the interaction. (see Docking
studies)
Linear combination of atomic orbitals (LCAO)
The linear combination of atomic orbitals (LCAO) is a mathematical
method used in quantum chemical calculations. It expresses the approximation
of the molecular orbital function as a linear combination of atomic orbitals
chosen as the basis functions.
Lipophilicity*
Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic
environment. It is commonly measured by its distribution behaviour in a
biphasic system, either liquid-liquid (e.g. partition coefficient in 1-octanol/water)
or solid-liquid (retention on reversed-phase high-performance liquid chromatography
(RP-HPLC) or thin-layer chromatography (TLC) system).
Lowest unoccupied molecular
orbital (LUMO) energy
The lowest unoccupied molecular orbital (LUMO) energy is obtained from
molecular orbital calculations and represents the electron affinity of
a molecule or its reactivity as an electrophile. (see Highest occupied
molecular orbital (HOMO) energy)
MINDO/3 calculations
MINDO/3 (Modified Intermediate Neglect of Differential Overlap)
calculations are semi-empirical MO calculations (Bingham
et al, 1975).
MM2 calculations
MM2 calculations involve molecular mechanical calculations using
version 2 of the widely-distributed force field program MM2 (Allinger,
1977).
MNDO calculations
MNDO calculations are semi-empirical molecular orbital (MO)
calculations, using a modified neglect of diatomic (differential) overlap
approximation.
MOL file format
The MOL file format is used to encode chemical structures, substructures
and conformations as text-based connection tables. It is used by MDL Information
Systems Inc. (e.g., in their MACCS or ISIS programs) (Dalby
et al., 1992).
Molar refractivity (MR)
The molar refractivity is the molar volume corrected by the
refractive index. It represents size and polarizability of a fragment or
molecule.
Molecular
connectivity index
A molecular connectivity index is a numeric descriptor derived from molecular
topology (Kier and
Hall, 1976).
Molecular descriptors
Molecular descriptors are terms that characterize a specific aspect of
a molecule (Van de
Waterbeemd and Testa, 1987).
Molecular design
Molecular design is the application of all techniques leading to the discovery
of new chemical entities with specific properties required for the intended
application.
Molecular
dynamics
Molecular dynamics is a simulation procedure consisting of the
computation of the motion of atoms in a molecule or of individual atoms
or molecules in solids, liquids and gases, according to Newton’s laws of
motion. The forces acting on the atoms, required to simulate their motions,
are generally calculated using molecular mechanics force fields. (see Molecular mechanics)
Molecular electrostatic potentials (MEP)
Molecular electrostatic potentials (MEP) are electrostatic properties
of a molecule based on the charge density as calculated directly from the
molecular wavefunction. The electrostatic potential (scalar with dimensions
of energy) is calculated at a point in the vicinity of a molecule. The
spatial derivative is the electric force (vector) acting on a unit positive
charge at that point caused by the nuclei and the electrons of the molecule
(Williams, 1991).
Molecular graphics*
Molecular graphics is a technique for the visualization and manipulation
of molecules on a graphical display device.
Molecular interaction potentials (MIP)
Molecular interaction potentials (MIP) are field properties arising from
the interaction of a probe (e.g., methyl, proton or water) with a molecule.
These are calculated in a space around the molecule.
Molecular lipophilic potentials (MLP)
Molecular lipophilic potentials are properties on the Van der
Waals or solvent accessible molecular surface or any other point in space
(e.g., in a 3D grid for CoMFA studies) calculated from atomic lipophilicity
contributions. It can be used for log P calculations, CoMFA and docking
studies (Gaillard et
al., 1994).
Molecular
mechanics
Molecular mechanics is the calculation of molecular conformational
geometries and energies using a combination of empirical force fields (Burkert
and Allinger, 1982).
Molecular mechanics - (synonymous with force field
method) - Method of calculation of geometrical and energy characteristics
of molecular entities on the basis of empirical potential functions (see
force field) the form of which is taken from classical mechanics. The method
implies transferability of the potential functions within a network of
similar molecules. An assumption is made on “natural” bond lengths and
angles, deviations from which result in bond and angle strain respectively.
Repulsive or attractive van der Waals and electrostatic forces between
nonbonded atoms are also taken into account.
Molecular modeling*
Molecular modeling is the investigation of molecular structures and properties
using computational chemistry and graphical visualization techniques in
order to provide a plausible three-dimensional representation under a given
set of circumstances.
Molecular orbital
(MO) calculations
Molecular orbital (MO) calculations are quantum chemical calculations based
on the Schrödinger equation, which can be subdivided into semi-empirical
and ab initio methods. (see Ab initio calculations)
Molecular orbital theory - An approach to molecular
quantum mechanics which uses one-electron functions (orbitals) to approximate
the full wavefunction.
Molecular shape
The molecular shape is an attribute of a molecule dealing with spatial
extension, form, framework, or geometry. It is often described by, e.g.,
principal axes, ovality, or connectivity indices. Molecular (dis-)similarity
Molecular (dis-)similarity is a number to express structural relatedness
between pairs of molecules, e.g., the so-called Carbo, Hodgkin or Tanimoto
coefficient (Good,
1992; Willett and Winterman, 1986).
Molecular topology Molecular topology
is the description of the way in which the atoms in a molecule are bonded
together. (see Molecular connectivity, Topological index)
Molfile
A molfile is a table containing atom type, connectivity and a more or less
arbitrary 2D or 3D information about a molecule. Well-known file formats
include the MOLfile used by MDL Information Systems Inc. (e.g., in the
database MACCS), the MOL2 file used by Tripos Associates (e.g., in the
modeling package SYBYL), or the CSSR format.
Monte Carlo technique
The Monte Carlo technique is a simulation procedure consisting of randomly
sampling the conformational space of a molecule.
Mulliken population analysis
Mulliken population analysis is a method for allocating electrons
to atoms in order to generate partial atomic charges. The results are strongly
dependent on the basis set used.
Mulliken population analysis - A partitioning scheme
based on the use of density and overlap matrices of allocating the electrons
of a molecular entity in some fractional manner among its various parts
(atoms, bonds, orbitals). As with other schemes of partitioning the electron
density in molecules, Mulliken population analysis is arbitrary and strongly
dependent on the particular basis set employed. However, comparison of
population analyses for a series of molecules is useful for a quantitative
description of intramolecular interactions, chemical reactivity and structural
regularities.
Multivariate statistics
Multivariate statistics is a set of statistical tools to analyze
data (e.g., chemical and biological) matrices using regression and/or pattern
recognition techniques.
Neural networks (see Artificial
neural networks)
Non-bonded energy terms Non-bonded energy terms are potential energy functions
describing van der Waals, electrostatic and hydrogen bonding interactions
in a force field.
Parameter space
The parameter space is a multidimensional space spanned by the descriptors
in a data set.
Partial least squares (PLS)
Partial least squares projection to latent structures (PLS)
is a robust multivariate generalized regression method using projections
to summarize multitudes of potentially colinear variables (Wold
et al., 1993).
Pattern recognition*
Pattern recognition is the identification of patterns in large data sets,
using appropriate mathematical methodology. Examples are principal component
analysis (PCA), SIMCA, partial least squares (PLS) and artificial neural
networks (ANN) (Rouvray,
1990; Van de Waterbeemd, 1995ab).
PCILO calculations
PCILO (Perturbative Configuration Interaction using Localized
Orbitals) calculations are semi-empirical molecular orbital calculations
related to CNDO/2 and MNDO calculations.
PDB
The Protein Data Bank (PDB) maintained at Brookhaven National Library,
Upton, New York, which contains X-ray structures of several hundreds of
proteins. (see PDB file)
PDB file A PDB (Protein Data Bank) file is an ASCII (American Symbolic Code for
Information Interexchange = text) file used to store the atomic coordinates
of a molecule, usually a protein or nucleic acid. (see PDB)
Pharmacophore generation
Pharmacophore generation is a procedure to extract the most
important common structural features relevant for a given biological activity
from a series of molecules with a similar mechanism of action.
PM3
PM3 is a widely used semi-empirical molecular mechanics program.
(see Molecular mechanics)
Principal components analysis (PCA)
Principal components analysis is a data reduction method using mathematical
techniques to identify patterns in a data matrix. The main element of this
approach consists of the construction of a small set of new orthogonal,
i.e., non-correlated, variables derived from a linear combination of the
original variables.
Principal properties
Principal properties are scales of substituent or amino acid
values derived by principal components analysis from a large matrix of
structure descriptor variables, and useful in series design and data analysis.
Quantitative structure-activity
relationships (QSAR)* Quantitative structure-activity relationships (QSAR) are mathematical relationships linking chemical structure and pharmacological
activity in a quantitative manner for a series of compounds. Methods which
can be used in QSAR include various regression and pattern recognition
techniques. QSAR is often taken to be equivalent to chemometrics or multivariate
statistical data analysis. It is sometimes used in a more limited sense
as equivalent to Hansch analysis. QSAR is a subset of the more general
term SPC (Kubinyi,
1993a).
Quantum chemical
calculations
Quantum chemical calculations are molecular property calculations based
on the Schrödinger equation, which take into account the interactions
between electrons in the molecule.
Receptor*
A receptor is a protein or a protein complex in or on a cell that specifically
recognizes and binds to a compound acting as a molecular messenger (neurotransmitter,
hormone, lymphokine, lectin, drug, etc). In a broader sense, the term receptor
is often used as a synonym for any specific (as opposed to non-specific
such as binding to plasma proteins) drug binding site, also including nucleic
acids such as DNA.
Receptor mapping* Receptor mapping
is the technique used to describe the geometric and/or electronic features
of a binding site when insufficient structural data for this receptor or
enzyme are available. Generally the active site cavity is defined by comparing
the superposition of active to that of inactive molecules.
Regression analysis
Regression analysis is the use of statistical methods for modeling
a set of dependent variables, Y, in terms of combinations of predictors,
X. It includes methods such as multiple linear regression (MLR) and partial
least squares (PLS).
Semi-empirical methods
Semi-empirical methods are molecular orbital calculations using
various degrees of approximation and using only valence electrons.
Semi-empirical quantum mechanical methods - The
methods which use parameters derived from experimental data to simplify
computations. The simplification may occur at various levels: simplification
of the Hamiltonian (e.g. as in the Extended Hückel method), approximate
evaluation of certain molecular integrals (see, for example, zero differential
overlap), simplification of the wave function (for example, use of p electron
approximation as in Pariser-Parr-Pople).
Sequential simplex method
The sequential simplex method is an experimental design method used for
the rapid optimization of properties.
SIMCA
The SIMCA (SIMple Classification Analysis or Soft Independent Modeling
of Class Analogy) method is a pattern recognition and classification technique
(Dunn and Wold, 1995).
Simulated annealing
Simulated annealing is a procedure used in molecular dynamics simulations,
in which the system is allowed to equilibrate at high temperatures, and
then cooled down slowly to remove kinetic energy and to permit trajectories
to settle into local minimum energy conformations.
Slater-type
orbitals (STO)
Slater-type orbitals are mathematical functions involving exponential functions,
used in ab initio quantum chemical calculations. These functions mimic
the electronic distribution in atoms and were used in ab initio calculations,
but have now been superceded by Gaussian-type orbitals. (see Gaussian-type
orbitals)
Slater type atomic orbital (STO) - The exponential
function on an atom; its radial dependence is given by Nrn-1 exp(-zr),
where n is the effective principal quantum number and z is the orbital
exponent (screening constant) derived from empirical considerations. The
angular dependence is usually introduced by multiplying the radial one
by a spherical harmonic Ylm(q,F).
SMILES
SMILES (Simplified Molecular Input Line Entry System) is a string notation
used to describe the nature and topology of molecular structures.
Solvent-accessible surface
The solvent-accessible surface is described as the surface traced out by
of a probe molecule, e.g., water, rolling over the van der Waals surface
of a molecule. There are two types: a) the surface formed by the locii
of the centre of a spherical probe rolled around a molecule in the van
der Waals contact and b) the contact surface (or Connolly/Richards surface).
(see Connolly surface)
STO-3G basis set
A STO-3G basis set is a set of Gaussian-type orbitals (GTO),
each of which uses three Gaussian functions to approximate a Slater-type
orbital (STO). More extended modern basis sets include STO-3-21G or STO-KG.
Structure-based design*
Structure-based design is a design strategy for new chemical entities based
on the three-dimensional (3D) structure of the target obtained by X-ray
or nuclear magnetic resonance (NMR) studies, or from protein homology models.
Structure-property correlations
(SPC) * Structure-property correlations (SPC) refers to all
statistical mathematical methods used to correlate any molecular property
(intrinsic, chemical or biological) to any other property, using statistical
regression or pattern recognition techniques (Van
de Waterbeemd, 1992).
Swain-Lupton parameters (F and R)
The Swain and Lupton parameters (F and R) are electronic field
and resonance descriptors derived from Hammett constants (Hansch
and Leo, 1979).
Taft steric parameter (Es)
The Taft steric parameter is a relative reaction parameter encoding
the reaction rate retardation due to the size of a substituent group.
Three-dimensional database searching
Three-dimensional database searching is a lead finding technique
using three-dimensional structures of compounds stored in a database.
Topliss tree*
A Topliss tree is an operational scheme for analog design (Topliss,
1972).
Topological
index A topological index is a numerical value associated with
chemical constitution for correlation of chemical structure with various
physical properties, chemical reactivity or biological activity. (see Molecular connectivity)
Topological index - The numerical basis for topological
indices is provided (depending on how a molecular graph is converted into
a numerical value) by either the adjacency matrix or the topological distance
matrix. In the latter the topological distance between two vertices is
the number of edges in the shortest path between these.
United atom approach
The united atom approach is a simplification used by molecular
mechanics programs such as AMBER and CHARMM which approximates the influence
of groups of atoms or molecular fragments by treating them as single atoms.
Verloop STERIMOL parameters
The STERIMOL parameters defined by Verloop are a set of substituent
length and width parameters (Verloop,
1987).
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Complementary and additional information may be found
in the following related documents:
- Glossary of Terms in Theoretical Organic Chemistry (V.I. Minkin)
- Guidelines for the Publication of Research Results from Empirical Force
Field Calculations (D.J. Raber)
- Best Values of Substituent Constants (J. Shorter)
- Acronyms used in Theoretical Chemistry (R.D. Brown)
Last Updated: March 15,2001
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