Chemaxon Descriptor Generation Toolkit

Optimizing ADMET predictions, pharmacokinetics and toxicity attributes are profound goals across all drug discovery projects. Exploit the power of machine learning methods on curated data sets to support the drug design and medicinal chemistry optimization with reliable models and predictions, targeting the elimination of cardiotoxicity risk during drug discovery.

• Continuous affinity prediction (pActivity=-log(Activity)) and classification
• State-of-the-art conformal prediction framework for error estimation
• Domain of applicability assessment: report on the top 5 most similar training data points
• Extendability: model can be re-trained with in-house data

Elemental Analysis provides fundamental molecular properties for general chemistry workflows and analytical scientists.

• Exact and nominal mass, molecular weight and atom count
• Elemental composition
• Molecular formulae
• Molecular composition
• Mass spectrum (isotope distribution) calculation

The partitioning of drugs in microscopic environments (e.g.: lipid bilayers of biological membranes) of different lipophilicity and hydrophilicity heavily influences its pharmacokinetic behavior. The partitioning is described by the logP and logD values of a drug, which are major descriptors in predicting ADMET properties.

The Partitioning calculator provides:

• LogP values using scientifically sound methods – LogP documentation
• LogD (pH vs. logD) plot – LogD documentation
• HLB (Hydrophilic Lipophilic Balance) number

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 the primary experimental technique to confirm and determine the chemical structure of organic compounds.

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

Structural Calculations provide:

• 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 ability to deal with molecular structures that have identical atomic composition, but different arrangement of bonds or spatial orientation is crucial in the identification, search and property calculation of compounds. Tautomerism, stereoisomerism and resonance are examples of isomerism.

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 Isomer calculator 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

Ionization has an essential impact on compound behavior in nearly all protic environments. On top of its application in general and analytical chemistry, relationships to drug pharmacokinetics and pharmacodynamics are well-established. Acidic and basic dissociation constants (pKa) and the microspecies distribution at different pH values are important to quantitatively describe ionization and comprehend physical and biological processes.

The Protonation calculator includes:

• Highly-accurate calculation of pKa values along with pH dependent distribution plots of relevant microspecies in water – pKa documentation
• Calculation of the major microspecies form at a given pH value – Major microspecies documentation
• Isoelectric point calculation

The Toolkit bundles are built to easily integrate with most systems using a range of different APIs including Java, Python, Microservices and .NET.