Glossary of Terms Used in Drug Design

Have you ever wondered what Conformational Analysis is? Or what the Rotarod Test measures? Below you will find brief definitions of the technical terms used throughout the Molecular Conceptor Learning Series, all of which are crucial to understanding the broad topic of drug design. The Molecular Conceptor Learning Series helps you to delve deeper and learn more about these topics; to download a demo, please click here.


3D-QSAR - A method for the establishment of a correlation between the biological activities and the fields produced in the surrounding of a molecule.

ADME - Absorption, Distribution, Metabolism, Excretion

Affinity - The affinity of a ligand is its ability to bind to its biological target.

Agonist - A chemical substance capable of activating a given receptor.

Amphipathic, amphiphile - With both hydrophilic and hydrophobic properties.

Analog - A molecule structurally similar to another, generally based on the same scaffold

Antagonist - A molecule that blocks the activation of a receptor.

Apo - 3D structure of a macromolecule without a ligand

Auto-correlation - The correlation of a variable with itself over successive time intervals (a mathematical tool used frequently in signal processing for amplification and interpretation of signals).

Benchmark - A dataset by which the validity of a method can be measured and judged.

Bidentate - Having two anchorage points

Binding mode - Orientation and geometry adopted by a chemical substance when it is bound to its receptor.

Bioactive conformation - The geometry adopted by a ligand when it binds to its biological target.

Bioavailability - The percentage of drug that is detected in the systemic circulation after its administration.

Bioisostere - A compound resulting from the exchange of a group of atoms with another and having similar biological properties to the parent compound.

Bioisosterism - The transformation of a molecule by the exchange of a group of atoms with another and having similar biological properties to the parent compound.

Cambridge Structural Database - The "Cambridge Structural Database". A worldwide repository source of experimental data on the X-ray structures of small molecules.

Chiral-switch - Development of single enantiomers of commercial racemate drugs.

Combinatorial library - A combinatorial library is a set of compounds prepared by combinatorial chemical synthesis.

Computational chemistry - A discipline based on mathematical models for the calculation or the simulation of molecular properties.

Conformational analysis - The study of the geometries and their associated energies for a given molecule.

Contour map - The 2D or 3D visualization of points that have the same value of a particular property and are connected together.

Descriptive QSAR - QSAR approach mainly focused on the interpretation of modeling molecular descriptors with the aim of explaining the mechanism of action. The predictions are generally reliable for congeneric chemicals (local models). This information can be used for the design of new chemicals.

Ee - stands for "enantiomeric excess". A quantity for measuring the optical purity and represents the percentage of the major enantiomer minus the percentage of the minor enantiomer

Enantiomer - Enantiomers are pairs of stereoisomers that are mirror images of one other

False positive - A hit that is erroneously recognized as good (positive).

FDA - Food and Drug Administration. Agency in the USA responsible for safety regulations.

Femtosecond - One quadrillionth (10-15) of a second of a second - a million times shorter than a nanosecond.

Force field - A set of mathematical equations and parameters used for assessing the energy of a given chemical system.

Genetic algorithm - A computerized search technique inspired by evolutionary biology and used in computer science to find approximate solutions to optimization and search problems.

Global minimum - The global minimum of a function is the smallest value it takes on over its entire range of possibilities

Harmonic - A function whose frequency is an integral multiple of the frequency of a reference function.

Heuristic - Set of rules to limit the search and increase the probability of solving a problem.

Holo - 3D structure of a macromolecule with a bound ligand

Homology Modeling - A method for predicting the 3D structure of a protein, based on its amino acid sequence and the 3D-structure of analog protein(s).

In silico - means using silicon-based computer technologies to perform simulations, modeling and experiments

Inhibitor - Chemical substance that blocks or suppress the activity of a given enzyme.

Isomers - Isomers are compounds with the same chemical formula but different 2D-structures

Ligand - In Biochemistry: substance that binds to a biological receptor. In Chemistry: an atom or group of atoms.

Microsecond - One millionth (10-6) of a second.

Minimization - Minimization treatments consists of successive alterations of the geometry of the molecule until a minimum is found on the conformational potential surface.

Moieties - Fragments, functional groups or portions of chemical compounds.

Molecular descriptor - Molecular descriptors are numerical values that capture the structure and properties of molecules

Molecular dynamics - Molecular dynamics (MD) is a computer simulation technique which follows the time evolution of a molecular system in 3D. Successive integration of Newtons equations of motion over time enables to obtain information about time-dependent properties of the system

Molecular mechanics - Molecular mechanics is a is a computer simulation technique for modeling the molecular geometry and energy of a system based on the energy minimization of its potential energy function. The set of potential functions used to calculate the energy is known as the force-field.

Molecular modeling, Molecular modelling - A field that models molecular behavior with theoretical methods and computational techniques.

Nanosecond - One billionth (10-9) of a second.

NCE - New Chemical Entity: a compound not previously described.

Nuclear Magnetic Resonance, NMR - An analytical method that allows the spectroscopic detection of structural information of molecules. It requires the application of a strong magnetic field.

Numerical integration - Numerical integration is the approximate computation of the analytical form of an integral using numerical techniques

Peptidomimetics - Compounds that are peptide mimetics. They have non-peptide structures in part or in full, and mimic the the pharmacological activity of peptides.

Pfam - The Pfam database contains information about protein domains and families.

Pharmacokinetics - The study of absorption, distribution, metabolism and excretion (ADME) of bioactive compounds.

Pharmacophore - Specific 3D arrangement of chemical groups common to active molecules and essential to their biological activities.

Picosecond - One trillionth (10-12) of a second.

Pixels - Surface element representing a value on a regular grid in 2D space.

Predictive QSAR - QSAR approach mainly focused on the prediction, reliability and applicability of QSAR to a large number of chemicals (even non congeneric) for screening purposes (non-local models). The validation parameters (also external) and the applicability domain are the principal points for attention.

Promiscuous - Some molecules emerge repeatedly as hits in diverse unrelated target systems. These so-called promiscuous hits act non-competitively, show little structure-activity relationships, and have poor selectivity.

Protein Data Bank - The "Protein Data Bank". A worldwide repository source of 3D structures of proteins obtained by X-ray crystallography or NMR studies.

Protein folding - A spontaneous process directed by the physical and chemical properties of the amino acid sequence that dictate the folding of a protein into a particular conformation.

QSAR, Quantitative Structure Activity Relationships - Quantitative Structure Activity Relationships (QSAR) - Mathematical equation linking chemical structure and biological activity for a series of compounds.

Quantitative Structure Property Relationships, QSPR - QSPR is an extension of QSAR and tries to formulate the relationship between structure and any molecular property in terms of a mathematical model.

Racemate - A racemate (or a racemic mixture) is a mixture of equal amounts of enantiomers

Relational database - A database where the data is arranged as a set of tables conforming to the relational model.

RMS - Root Mean Square: the square root of the arithmetic average of the square's set of values.

RMSD - The Root Mean Square Deviation is a measure of the differences between values predicted and values experimentally observed.

Rotarod test - Test measuring the performance of mice staying on a rotarod apparatus. Control mice are trained and can to stay for example for 120 seconds on a rod rotated at 12 revolutions per min.

Spin-spin coupling - The interaction between the spin magnetic moments of different particles (electrons, nuclei) that gives a detectable signal in NMR (multiplet patterns).

Statistical mechanics - A method that treats the detailed state of a system as an ensemble subject to statistical uncertainties. It can be used to derive thermodynamic properties from properties at the molecular level.

Stochastic - Stochastic means "random" in opposition to "deterministic" (where random phenomena are not involved). Stochastic models are based on random trials that are guided by computerized stochastic algorithms.

Stochastic algorithm - Process with random variables

Structural biology - Structural Biology is a new field of modern biology dedicated to the determination of the 3D structure of biological proteins to give insight to the function of these macromolecules in the living cell and to exploit this knowledge for the design of new drugs.

Structure-activity relationships - Structure-Activity Relationships (SAR) is the analysis of the relationships between chemical structure and biological activity.

Toxicophore - A toxicophore is a structural fragment known to be related to some biological toxicity

Trajectory - Trajectory = positions + velocities.

Transition state analog - A molecule that mimics the transition state of an enzymatic reaction.The transition state is an intermediate high energy conformation that all substrates must pass though during a reaction. This state normally prevents the spontaneous conversion of substrate to product and is usually stabilized by the enzyme involved.

Ubiquitous - Play different roles, at the same time.

Virtual library - A library which exists solely in electronic form (or on paper) and used in the design and evaluation of possible real libraries.

Voxels - Volume element representing a value on a regular grid in 3D space.