5-Chemistry-Biochemistry-Drug-Activity-Methods

Active Analog Approach

Rules {Active Analog Approach} can align molecule activities by analogous structures.

active pharmaceutical

Rules can align molecule activities by structural group {active pharmaceutical ingredient} (API).

alternating conditional expectations

Non-parametric methods {alternating conditional expectations} (ACE) can analyze activity.

artificial neural network

Input "neuron" layer can hold physico-chemical properties and feed to middle layer using sigmoidal function {transfer function} with weights for outputs. Middle-layer "neurons" feed to one output {artificial neural network} (ANN).

chemometrics

Mathematical tools {chemometrics} applied to structure-activity relationships can find correlations and regression, recognize patterns, classify compounds and properties, design experiments for random screening and measuring, and validate results.

computer assisted metabolism prediction

Quantum mechanics can pair with empirical approaches {computer-assisted metabolism prediction} (CAMP).

deconvolution in arrays

Cell arrays can pool more than one sample in cells, which allows fewer cells. Methods {deconvolution} can track sample pooling.

convolution

Convolution puts each sample into several cells, in regular pattern. Testing looks for one effect. Some cells show effect, but most do not. If sample causes effect, all cells with that sample show effect. Cells that contain that sample form pattern, so pattern indicates sample name.

deconvolution

Deconvolution uses convolution method and resulting cell pattern to find sample name. For example, for 100-cell array, 10 samples can feed into 90 cells, each cell receiving two samples. Ten cells have control samples. See Figure 1. Samples are in 18 cells. If testing shows that all 18 have activity over threshold, then that sample is effective.

If sample interactions cause effect, deconvolution can find interactions. If testing shows that only one cell has activity over threshold, those two samples must interact to be effective.

empirical-quantum chemical

Combining quantum mechanics and physico-chemical properties {empirical-quantum chemical} {combined empirical/quantum chemical approach} can predict chemical behavior.

Korzekwa-Jones model

Models {Korzekwa-Jones model} can be for P-450 hydrogen abstraction and depend on difference between radical free energy and hydrogenated-atom free energy, as well as radical ionization potential and constant additive term.

Lennard-Jones potential

Steric effects and van der Waals forces can cause fields {Lennard-Jones potential}.

loading plot

Plots {loading plot} can use variable weights.

modified neglect of differential overlap

Semiempiric methods {modified neglect of differential overlap} (MNDO) can ignore overlap.

molecular modeling

Molecule-modeling programs {molecular modeling}, such as Alchemy III and SYBYL from Tripos, can use electrostatics or quantum mechanics.

non-linear partial least-squares

Non-parametric methods {non-linear partial least-squares, drug} (NPLS) can find least squares.

non-parametric method

Response-surface methods {non-parametric method}, such as ACE, NPLS, and MARS, can be non-parametric.

rule induction system

IF/THEN statement sets {rule induction system, drug} can make output from input.

score plot

Graphs {score plot} can plot compound activities.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Clustering

cluster analysis drug

In multidimensional property space, compound clusters make classes separated by distance {cluster analysis} (CA). CA reduces unimportant variables. Substructure, topological index, physico-chemical property, calculated physico-chemical property, or hydrophobicity can determine classes.

cluster significance

Using discrete or continuous data and embedded data can put compounds into groups by activity level {cluster significance analysis} (CSA). CSA locates small clusters in large spaces.

Cone and Hodgkin similarity index

Methods {Cone and Hodgkin similarity index} can measure molecular similarity.

discriminant-regression model

Models {discriminant-regression model} (DIREM) can locate small clusters in large spaces.

distance-b program

Methods {distance-b program} (EVE) can locate small clusters in large spaces.

hierarchical cluster

Unsupervised methods {hierarchical cluster analysis} (HCA) can measure distances between all points and make point vs. distance dendograms.

Jarvis-Patrick method

Structures can cluster in large databases by rating different compounds by similarity {Jarvis-Patrick method}.

k-nearest neighbor

Supervised methods {k-nearest neighbor} (k-NN) can calculate new-object distances from all other objects, to locate small clusters in large spaces.

partitioning

Processes {partitioning} can merge individuals into groups or split whole into clusters.

similarity measure

Values {similarity measure} can compare distances.

single class discrimination

Methods {single class discrimination} (SCD) can locate small clusters in large spaces.

supervised method

Classifications {supervised method} can use already known patterns and clusters.

trend vector analysis

Activity and descriptor correlation vectors {trend vector analysis} can rank compound similarity.

Ward clustering method

Hierarchical methods {Ward's clustering method} {Ward clustering method} can agglomerate compounds to find clustering.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Clustering-SIMCA

Soft Independent Modeling of Class Analogies

Supervised methods {Soft Independent Modeling of Class Analogies} (SIMCA) can use region-boundary or envelope models, to locate small clusters in large spaces.

class analogy

Clustering methods {class analogy} can be SIMCA methods.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Clustering-Distance

city-block distance

Distance measures {city-block distance} between structure-space points can be the same as Manhattan distance.

Manhattan distance

Distance measures {Manhattan distance} between structure-space points can be the same as city-block distance.

Minkowski distance

Distance measures {Minkowski distance} between structure-space points can be the same as Lp-metric.

Lp-metric

Distance measures {Lp-metric} between structure-space points can be the same as Minkowski distance.

Mahalanobis distance

Structure-space points have distances {Mahalanobis distance}.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Clustering-Linkage

centroid linkage

Hierarchical methods {centroid linkage} that agglomerate compounds can find clustering.

complete linkage

Hierarchical methods {complete linkage} that agglomerate compounds can find clustering.

single linkage

Hierarchical methods {single linkage} that agglomerate compounds can find clustering.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Factor Analysis

factor analysis

Processes have factors {factor analysis}. Physico-chemical or structural properties describe compounds and have components {descriptor, factor} {X-variable, factor} {X descriptor, factor}. Chemical activities relate to variables {response variable}.

canonical factor analysis

Methods {canonical factor analysis} can be for factor analysis.

centroid method

Methods {centroid method} can be for factor analysis.

combinatoric QSAR

QSAR {combinatoric QSAR} can find similarities using different descriptor combinations.

Comparative Molecular Moment Analysis

Moments of inertia, and dipole and quadrupole moments, can be descriptors to calculate molecular moments {Comparative Molecular Moment Analysis} (CoMMA). CoMMA depends on shapes and charges.

Correlation Analysis

Properties and structures have relations {Correlation Analysis}.

correspondence analysis

Factor-analysis methods {correspondence analysis} {correspondence factor analysis} (CFA) can use variable frequencies relative to activities, finds chi-square values, and finds principal components.

disjoint principal component

Principal components {disjoint principal component} (DPP) can be independent.

eigenvalue-one criterion

Thresholds {eigenvalue-one criterion} can be how many components have eigenvalues greater than one.

eigenvector projection

Unsupervised linear methods {eigenvector projection} can find factors.

Evolutionary Programming

Models {Evolutionary Programming} (EP) can add and subtract randomly selected variables, with crossing-over, and evaluate for "fitness" or best fit.

evolving factor analysis

Methods {evolving factor analysis} (EVA) can analyze ordered data.

explained variance percentage

Methods {percentage of explained variance} {explained variance percentage} can indicate number of components required to reach 90% of total variance.

extrathermodynamic approach

Parameters and descriptors can linearly relate to free energy {extrathermodynamic approach}.

free energy perturbation

Factor-analysis methods {free energy perturbation} (FEP) can use free-energy changes.

Free-Wilson approach

Binary descriptors can note molecule-substructure presence or absence {Free-Wilson approach}.

Genetic Function Algorithm

Linear property sets can have different values, change values by crossing-over between related such genes, and have random change {Genetic Function Algorithm} (GFA), to select best fit.

Hammett sigma value

Values {Hammett sigma value} can relate to electronic and electrostatic properties.

Hansch equation

Activity, partition coefficients for hydrophobicity, ionization degree, and molecular size relate {Hansch equation}.

latent variable

Variables {latent variable} can be linear-descriptor combination.

linear discriminant analysis

Supervised methods {linear discriminant analysis} (LDA), in which boundary surface minimizes region variance and maximizes variance between regions, can put compounds into groups by activity level.

linear free energy

log K = k1 * sigma + k2 {linear free energy equation, drug} (LFE).

linear learning machine

Supervised methods {linear learning machine} (LLM) can divide n-dimensional space into regions, using discriminant function.

maximum-likelihood method

Factor-analysis methods {maximum-likelihood method} can find factors.

multidimensional scaling

Metric or non-metric methods {multidimensional scaling} (MDS) can analyze similarity or dissimilarity matrices to find dimension number and place objects in proper relative positions.

multivariate adaptive regression spline

Non-parametric methods {multivariate adaptive regression spline} (MARS) can find factors.

Mutation and Selection Uncover Models

Models {Mutation and Selection Uncover Models} (MUSEUM) can add and subtract randomly selected variables, with no crossing-over, and evaluate for "fitness" or best fit.

non-linear iterative partial least-squares

Unsupervised linear methods {non-linear iterative partial least-squares} (NIPALS) can represent data as product of score matrix, for original observations, and loading-matrix transform, for original factors.

non-linear mapping

Topological mappings {non-linear mapping} (NLM) can be factor-analysis methods in which linear-variable combinations make two or three new variables.

predictive computational model

Information about compound physico-chemical properties can predict compound chemical or physiological behavior in vitro and in vivo {predictive computational model}.

principal component analysis

Variables {principal component} (PC) can be linear-descriptor combinations. Unsupervised linear method {principal component analysis, factor} (PCA) represents data as product of score matrix, for original observations, and loading-matrix transform, for original factors. PCA is factor-analysis method in which linear variable combinations make two or three new variables. PCA reduces unimportant variables.

principal component regression

Singular-value decomposition (SVD) can find best singular values for predicting {principal component regression} (PCR). SVD projects regression to latent structures.

principal factor analysis

Modified PCA {principal factor analysis} can find principal factors.

Procrustes analysis

Methods {Procrustes analysis} can identify descriptor sets for describing similarity.

QR algorithm

Methods {QR algorithm} can diagonalize matrices.

rank annihilation

Unsupervised linear methods {rank annihilation} can find factors.

Scree-plot

Residual variance approaches constancy {Scree-test, drug}, and plotted slope levels off {Scree-plot}, depending on component number.

singular value decomposition

In unsupervised linear methods {singular value decomposition, drug} (SVD), correlation matrix is product of score, eigenvalue, and loading matrices, with diagonalization using QR algorithm.

spectral mapping analysis

Factor-analysis methods {spectral mapping analysis} (SMA) can first take data logarithm to eliminate outliers and then subtract means from rows and columns, to leave only variation, showing which variables are important and how much.

structure space

Spaces {structure space} can have two or three principal components.

target-transformation

Methods {target-transformation factor analysis} can rotate features to match known pattern, such as hypothesis or signature.

Unsupervised Method

Factors and response variable have relations {Unsupervised Method}, without using factor information or predetermined models.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Factor Analysis-Design

factorial design

Designs {factorial design} can try to ensure design-space sampling, if position varies.

fractional factorial

Designs {fractional factorial design} can try to ensure design-space sampling, if position varies.

response surface method

Three-level designs {response surface method} (RSM) can have three factors that quantify relationships among responses and factors. RSM includes MLR, OLS, PCR, and PLS linear designs; non-linear regression analysis (NLR); and non-parametric methods, such as ACE, NPLS, and MARS.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Isomer Enumeration

Cayley tree structure

isomer-enumeration method {Cayley tree structure}.

CONGEN program

Isomer-enumeration methods {CONGEN program} can be successors to DENDRAL.

DENDRAL program

Isomer-enumeration methods {DENDRAL program} can be forerunners of CONGEN.

Henze and Blair recursion formulas

isomer-enumeration method {Henze and Blair recursion formulas}.

Polya enumeration theorem

Isomer-enumeration methods {Polya's enumeration theorem} {Polya enumeration theorem} can use group theory.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Molecular Orbital

molecular orbital

Electron orbitals {molecular orbital} can be for whole molecule.

ab initio analysis

Analyses {ab initio analysis} can use all electrons.

linear combinations of atomic orbitals

Adding atomic orbitals can approximate molecular orbitals {linear combinations of atomic orbitals} (LCAO).

perturbative configuration interaction

Semiempiric methods {perturbative configuration interaction using localized orbitals} (PCILO) can use perturbations.

semiempiric

Analyses {semiempiric} can use valence electrons and parameterize core electrons.

simple delta index

Sigma electrons can contribute {simple delta index, drug}.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Regression

regression for drugs

Factors, properties, or structures {regressor} can contribute to response values {regression, regressor} {Regression Analysis}.

canonical correlation

Regression can project to latent structures {canonical correlation} (CC), to put compounds in classes.

continuum regression

Regression {continuum regression} (CR) can project to latent structures, to put compounds in classes.

correlation matrix

Variance-covariance matrix {correlation matrix, drug} can scale to normalize data.

kernel algorithm

Regression can project to latent structures {kernel algorithm}, to put compounds in classes.

matrix diagonalization

Methods {matrix diagonalization, drug} can simplify data variance-covariance matrix.

non-linear regression

Parametric methods {non-linear regression} (NLR) can find descriptor coefficients by non-linear regression.

ridge regression

Regression can project to latent structures {ridge regression} (RR), to put compounds in classes.

Spearman rank correlation coefficient

Methods {Spearman rank correlation coefficient} can measure molecular similarity.

variance-covariance matrix

Complete, symmetric, square matrix {variance-covariance matrix} uses property values and structure values.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Regression-Least Squares

adaptive least-squares

Regression can project to latent structures {adaptive least-squares} {ALS algorithm}, to put compounds in classes.

classical least-squares

Methods {classical least-squares, drug} (CLS) can be the same as ordinary least-squares analysis.

Comparative Molecular Field Analysis

Partial least-squares {Comparative Molecular Field Analysis} (CoMFA) can analyze grid around site atom and find grid-point electrostatic and steric interactions, to make sampled-point descriptors.

fuzzy adaptive least

Compounds have different classes with different weights {fuzzy adaptive least-squares} (FALS).

Generating Optimal Linear PLS Estimations

Methods {Generating Optimal Linear PLS Estimations} (GOLPE) can use PLS and D-optimal design to select variables, and cross-validates.

inverse least-squares

Fitting methods {inverse least-squares} (ILS) can find regression line.

least-squares regression

Methods {least-squares regression, drug} can be the same as ordinary least-squares analysis.

linear least-squares

Methods {linear least-squares regression, drug} can be the same as ordinary least-squares analysis.

matrix bidiagonalization method

Partial least-squares methods {matrix bidiagonalization method, drug} can simplify data variance-covariance matrix.

multi-block PLS

Regression can project to latent structures {multi-block PLS}, to put compounds in classes.

multiple least-squares regression

Methods {multiple least-squares regression, drug} can be the same as ordinary least-squares analysis.

multiple linear regression

Methods {multiple linear regression} (MLR) can measure linear component dependence on physico-chemical or structural properties and finds descriptor coefficients.

multivariate least-squares regression

Methods {multivariate least-squares regression, drug} can be the same as ordinary least-squares analysis.

non-least-squares

Methods {non-least-squares} (NLS) can detect non-linear relationships.

ordinary least-squares

Fitting methods {ordinary least-squares} (OLS) can find descriptor coefficients.

partial least-squares

Methods {partial least-squares} (PLS) can use least-squares to find independent variables and dependencies among variables. It projects regression to latent structures. It maximizes latent-variable and observable covariation. It diagonalizes the matrix.

SAMPLS algorithm

Methods {SAMPLS algorithm} can apply PLS to trend vector analysis.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Statistical

best linear unbiased estimator

Estimates {best linear unbiased estimator} (BLUE) can give smallest variance among estimators.

standard error

Error measures {standard error} can be square root of MSE.

5-Chemistry-Biochemistry-Drug-Activity-Methods-Statistical-Squares

squares of differences

SSE, SSR, or SST {sum of squares of differences} {squares of differences sum}.

mean square error

SSE / (observation number + factor number - 1) {mean square error} (MSE).

SSE

Errors or residuals can cause sum {SSE} of squares of differences between observed and predicted responses.

SSR

Regression can cause sum {SSR} of squares of differences between observed and mean.

SST

Sum {SST} of squares of differences between predicted and mean makes total: SST = SSE + SSR.

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Date Modified: 2022.0225