Calculators and Predictors
High-quality physico-chemical calculations and predictions for drug discovery
The behavior of drugs in the different biological processes of the human body is governed by the molecular structure. This behavior can be described by important physico-chemical properties of the drug molecule. Optimization of these properties plays a crucial role in driving forward the different phases of drug discovery and design.
The Calculators & Predictors offer a wide range of chemical calculations that are available from multiple endpoints, combining great availability, consistency and integration options. From easy-to-use plugins to fully customizable command line tools, the Calculators & Predictors are available via all main ChemAxon products. Extensive API and training options provide further possibilities for integration and customization. A brief summary of the available calculations is listed below.
ADMET Plugin Group
Optimizing pharmacokinetics and toxicity attributes are profound objectives across all drug discovery projects. The new ADMET plugin exploits the power of machine learning methods on curated data sets to support the drug design and medicinal chemistry optimization with reliable models and predictions.
The first released end-point is targeting the elimination of cardiotoxicity risk during drug discovery by predicting hERG inhibition.
- Continuous affinity prediction (pActivity=-log(Activity)) of the hERG inhibition
- State-of-the-art conformal prediction framework for error estimation
- Domain of applicability assessment: report on the top 5 most similar training data
- Extendability: model can be re-trained with in-house data
Elemental Analysis provides calculations of the most basic molecular properties:
- Molecular weight and atom count
- Elemental composition
- Molecular formulae
- Molecular composition
Mass spectrum (isotope distribution) calculation is also available. Elemental Analysis documentation
The importance of ionization in drug pharmacokinetics and pharmacodynamics is well-established in the relevant scientific literature. Knowing the acidic/basic dissociation constants (pKa) and the microspecies distribution of a drug molecule at different pH values are important to quantitatively describe ionization.
The Protonation bundle includes:
The partitioning of drugs in microscopic environments (e.g.: lipid bilayers of biological membranes) of different lipophilicity and hydrophilicity heavily influences its pharmacokinetic behaviour. The partitioning is described by the logP and logD values of a drug, which are major descriptors in predicting ADMET properties.
The Partitioning bundle provides calculation of:
Solubility in water (commonly referred to as logS) is one of the most important parameters to achieve for desired pharmacological response. Any drug to be absorbed must be present as a solution at its site of absorption.
As the majority of drugs are molecules that have ionizable groups, the solubility of the compound depends highly on the pH environment. The Solubility Predictor is able to predict:
- Intrinsic (thermodynamic) solubility in water
- pH-dependent solubility (pH-logS plot)
- A qualitative solubility category
Nuclear Magnetic Resonance spectroscopy is an experimental research technique used by scientists to determine chemical structure of molecules.
As NMR spectrometers are relatively expensive, predicting NMR spectra for a set of possible structures and comparing them with experimental data is a well established approach to facilitate structure elucidation. The NMR Predictor is able to:
- Predict 13C and 1H NMR spectra for molecules composed of the most frequent elements (H, C, N, O, F, Cl, Br, I, P, S, Si, Se, B, Sn, Ge, Te and As)
- Import and display NMR spectra from JCAMP-DX files
Isomerism is an interconversion between molecules that have identical atomic composition, but different arrangement of bonds or spatial orientation. Tautomerism, stereoisomerism and resonance are examples of these inter-conversions.
Tautomerization can affect identification, searching and physico-chemical properties of molecules. Stereoisomers have the same physico-chemical properties (e.g.: melting point, solubility), but they differ in pharmacokinetic and pharmacodynamic behavior. Resonance describes the rearrangement of delocalized electrons in the molecule, which results in a set of contributing structures of the original structure.
The Isomers bundle can:
- Generate different tautomer sets useful for searching and tautomer handling
- Calculate tautomer distribution and major tautomer form in water
- Generate tetrahedral and double-bond stereoisomers starting either from a 2D or 3D structure
- Generate resonance structures
The Structural Calculations bundle provides different structural calculations including:
- Hydrogen Bond Donor/Acceptor (HBDA) count
- 2D topological descriptors
- 3D geometrical descriptors
- Molecular surface calculations
- 3D conformer generation, molecular dynamics
- 3D Alignment
- Different electron structural property calculations
The versatile Calculators & Predictors technology is available through a number of other applications and can be accessed in multiple ways. It is available as:
- Plugins integrated in Marvin
- Calculations on Chemicalize
- Functions in JChem for Office
- Command line tool cxcalc
- Chemical Terms functions in JChem Engines, Instant JChem, JChem for Office, Compound Registration or Reactor
- Calculator nodes in KNIME and components in Pipeline Pilot
- Java API
- WebServices API