PASS - Pharmacology Software

The acronym PASS stands for Prediction of Activity Spectra for Substances. After entering structural formulas of organic compounds - either a single structure or a big library - the program instantly gives a list of predicted bioactivities, accompanied by estimated mathematical probabilities.
Details

Key features of PASS:
• Chemical structures are represented with Multilevel Neighborhood of Atoms (MNA) descriptors
• Activity spectra for libraries of compounds can be predicted within minutes
• Atoms of every structure are colored according to their contribution to the chosen activity
• Possibility to create and train own SAR bases and to modify the included SAR base
• Currently, 4,444 bioactivities can be predicted with the included SAR base
• Mathematical algorithm based on Bayesian estimates of probabilities

PASS can quickly predict biological activity spectra for organic drug-like compounds qualitatively. The activities that can be predicted range from pharmacotherapeutic effects, biochemical mechanisms and toxic and adverse effects to influence on the metabolism, gene regulation and transporter-related activities. The software runs under Windows.

PASS has been developed by Vladimir Poroikov, Dmitry Filimonov & Associates currently working in the Department for Bioinformatics at the Institute of Biomedical Chemistry, Russian Academy of Medical Sciences in Moscow.

A free demo version, as well as further information, is available upon request.

Software Link :  PASS - Pharmacology Software

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Softwares in Pharmacology - CalcuSyn Version 2.0

CalcuSyn Version 2.0 is the definitive analyzer of combined drug effects, able automatically to quantify phenomena such as synergism and inhibition. Mixed drug treatment is becoming common in the treatment of cancer, AIDS etc, and CalcuSyn is the most widely used software for establishing efficacy in this field. It performs multiple drug dose-effect calculations using the Median Effect methods described by T-C Chou and P. Talalay (Trends Pharmacol. Sci. 4, 450-454).

CalcuSyn can easily be integrated with other software. Data can be entered via the keyboard or file import either into the grid or directly into the analysis engine. When the grid is used, data can be processed through wizards which make the software easily accessible to new users.

Data can be processed both for individual drugs and for constant-ratio or non-constant-ratio combinations of drugs. CalcuSyn automatically graphs the data and produces reports giving summary statistics on all drugs plus detailed analysis of drug interactions including the Combination Index and EDx (for any value of x). Estimates of accuracy of EDx and CI can be calculated with Monte Carlo simulations or by a highly accurate algebraic estimation algorithm. The plots drawn by CalcuSyn include dose-effect, median-effect, isobolograms and CI-effect. All data and results are easily accessible by mouse-click on the contents tree.

CalcuSyn Version 2.0 has Undo and Redo tools. There are flexible arrangements for printing of results and graphs and their export to spreadsheets, wordprocessors, graphics packages etc. A comprehensive manual is supplied as .pdf with the software and there is a detailed Help file. These give a thorough account of the theoretical basis of the analysis methods including the statistical treatment of results. Already used in hundreds of academic labs and pharmaceutical companies, CalcuSyn is indispensable for the study of drug mixtures.

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Strike - Drug design software

Strike (Statistical tool for revealing insight and knowledge) is a statistical modeling package designed especially for chemists. An easy-to-use interface and wide variety of property prediction tools combine to make Strike a powerful tool for developing structure-activity relationships.

Details

The preparation of hit-rich virtual libraries can be a time-consuming and challenging process. Incorrect characterization of drug-like properties will result in low HTS payoffs, with fewer, less promising hits. While scores of 2D and 3D descriptors can be rapidly calculated or predicted, these properties are of limited use unless they are correlated with drug action. Furthermore, in order to protect against over-fitting, any predictive relationship must use only a reasonable subset of descriptors with minimal covariance.

Quantitative structure-activity relationships (QSAR) and statistical modeling can be used to develop such predictive relationships, greatly improving the profile of virtual libraries. Chemically aware statistical modeling software combines sophisticated analysis tools with the ability to easily visualize the structures and properties used to derive a structure-activity relationship. QSAR is one of the most mature techniques in rational drug design, and has repeatedly proven itself to be a low-cost, high-return investment. 

 

Software Link : Strike - Drug design software

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QM-Polarized Ligand Docking software

The first such algorithm of its kind, QM-Polarized Ligand Docking uses ab initio methodology to calculate ligand charges within the protein environment. Innovative and practical, QM-Polarized Ligand Docking offers substantially enhanced accuracy over pure MM docking algorithms.

Details

Accurate treatment of electrostatic charges is crucial to the success of any docking algorithm. Although contemporary force fields are capable of modeling partial atomic charges on ligands with reasonable accuracy, they are generally incapable of considering charge polarization induced by the protein environment. The greater the role charge polarization plays in determining a ligand's bound conformation, the more difficult it will be for MM docking algorithms to perceive the correct binding mode. For research applications that demand the highest level of docking accuracy, Schrodinger introduces QM-Polarized Ligand Docking (QPLD), which uses ab inito charge calculations to overcome this limitation.

QPLD combines the docking power of Glide with the accuracy of QSite, Schrodinger's respected QM/MM software. The QPLD algorithm begins with a Glide docking job that generates several geometrically unique protein-ligand complexes. QSite then performs a single-point energy calculation on each complex, treating the ligand with ab initio methods and deriving partial atomic charges using electrostatic potential fitting. Glide then re-docks the ligand using each of the ligand charge sets calculated by QSite, and the QPLD algorithm returns the most energetically favorable pose. The fully automated algorithm is calibrated to provide useful default settings that can be modified at the user's discretion.

In keeping with Schrodinger's tradition of pairing innovation and practicality, QPLD calculations are effortlessly set up and launched using a single panel within the Maestro interface. Calculations are easily parallelized across multiple processors, and results are automatically incorporated into Maestro for visualization and analysis. 

 

Software Link: QM-Polarized Ligand Docking software

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PharmaExper - Drug design software

PharmaExpert analyzes the relationships between biological activities, the interactions of drugs and the multiple targeting actions of chemical compounds. As a pharmacological knowledge-based tool, it provides in silico screening of compounds using PASS prediction results.

Details

Key features of PharmaExpert:
• Mechanism-effect relationship (MER) base, manually curated by experts, contains 11,049 mechanism-effect relationships
• Selection of compounds with required therapeutic but without side effects
• Comparative analysis of compounds with similar structures
• Selection of compounds with multiple mechanisms of action
• Analysis of drug-drug interactions with regard to their pharmacokinetic, pharmacodynamic and adverse effects

PharmaExpert is an addition to the PASS (Prediction of Activity Spectra for Substances) tool. It provides a comfortable solution for data mining of the PASS prediction results to find the best drug-like candidates from a set of compounds. The core of the program is a mechanism-effect relationship (MER) base, manually curated by experts, which is used to determine cause-effect relationships for the compounds. Like PASS, the software runs under Windows.

PharmaExpert has been developed by Vladimir Poroikov, Dmitry Filimonov & Associates currently working in the Department for Bioinformatics at the Institute of Biomedical Chemistry, Russian Academy of Medical Sciences in Moscow (http://www.pharmaexpert.ru/PASSOnline/).

A free demo version, as well as further information, is available on our homepage.

Software Link: PharmaExper - Drug design software

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LigPrep - Ligand Analysis Software

LigPrep goes far beyond simple 2D to 3D structure conversions by including tautomeric, stereochemical, and ionization variations, as well as energy minimization and flexible filters to generate fully customized ligand libraries that are optimized for further computational analyses.

Details

Computational methods have become an indispensable part of lead identification efforts. Nearly all methods require accurate 3D molecular models as a starting point. However, many corporate and purchasable compound databases contain only 2D molecular structures. Efficient and accurate 2D to 3D conversion is therefore a key precursor to computational analyses.

Beyond simple one-to-one structural conversion, it is equally important to generate scientifically sound molecular models that enumerate the different structural and chemical possibilities a ligand could sample, as these variations could lead to dramatically different results in subsequent computations. A versatile conversion program that can be configured to generate ligand libraries with the desired structural and chemical features can significantly streamline the entire in silico drug discovery process. 

 

Software Link: LigPrep - Ligand  Analysis Software

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Epik - Drug design software

Combining the proven reliability of Hammett and Taft methods with powerful tautomerization tools, Epik is the program of choice for accurate enumeration of ligand protonation states in biological conditions.

Details

Proper treatment of ligand protonation states is essential to lead discovery. The pKa's of a drug's various functional groups play a critical role in determining its bioavailability and pharmacokinetic profile, while virtual screening software relies on correctly protonated structures in order to perceive the discrete interactions that drive ligand binding. However, many readily available libraries provide ligand structures in familiar tautomeric forms with all functional groups neutralized. These forms may not be highly populated under biological conditions, and are therefore inappropriate for property prediction or virtual screening experiments.

Epik provides a time-tested solution to these problems, designed specifically to work within the context of contemporary drug discovery workflows. Using Hammett and Taft methods in conjunction with ionization and tautomerization tools, Epik is able to rapidly and reliably predict pKa values and return all chemically sensible structures.

Software Link : Epik - Drug design software

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PASS - Drug design software

The acronym PASS stands for Prediction of Activity Spectra for Substances. After entering structural formulas of organic compounds - either a single structure or a big library - the program instantly gives a list of predicted bioactivities, accompanied by estimated mathematical probabilities.

Details

Key features of PASS:
• Chemical structures are represented with Multilevel Neighborhood of Atoms (MNA) descriptors
• Activity spectra for libraries of compounds can be predicted within minutes
• Atoms of every structure are colored according to their contribution to the chosen activity
• Possibility to create and train own SAR bases and to modify the included SAR base
• Currently, 4,444 bioactivities can be predicted with the included SAR base
• Mathematical algorithm based on Bayesian estimates of probabilities

PASS can quickly predict biological activity spectra for organic drug-like compounds qualitatively. The activities that can be predicted range from pharmacotherapeutic effects, biochemical mechanisms and toxic and adverse effects to influence on the metabolism, gene regulation and transporter-related activities. The software runs under Windows.

PASS has been developed by Vladimir Poroikov, Dmitry Filimonov & Associates currently working in the Department for Bioinformatics at the Institute of Biomedical Chemistry, Russian Academy of Medical Sciences in Moscow (http://www.pharmaexpert.ru/PASSOnline/).

A free demo version, as well as further information, is available on our website. 

 

Software Link: PASS - Drug design software

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Desmond - Drug design software

Desmond's combined speed and accuracy make possible long time scale molecular dynamics simulations, allowing users to examine events of great biological and pharmaceutical importance. Seamlessly integrated with Maestro, Desmond provides comprehensive setup, simulation, and analysis tools.

Details

Biological systems are dynamic in nature; analyzing their motion at the molecular and atomistic level is therefore essential to understanding key biological phenomena. For decades, there has been keen interest in modeling the dynamic aspects of protein structure and function, and molecular dynamics (MD) simulation stands alone as the fundamental computational tool for capturing dynamic events of scientific interest and pharmaceutical relevance. More recently, static structure-based approaches, such as docking and virtual screening, have made important strides in advancing drug discovery. MD, especially when coupled with these other computational tools, will open the door to addressing the many drug discovery problems for which the dynamic nature of proteins cannot be ignored, as in the mechanisms of highly mobile membrane proteins and in ligand-induced conformational changes of active sites.

Many biological phenomena of scientific and pharmaceutical interest occur on time scales that are computationally demanding to simulate. A high-performance MD code, together with continuously advancing computer hardware technologies, can be used to perform simulations on time scales that illuminate these important biological processes. Desmond, a newly developed MD code created by D. E. Shaw Research, provides an unprecedented combination of parallel scalability, simulation throughput, and scientific accuracy to achieve these goals. 

 

Software Link : Desmond - Drug design software

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Core Hopping - Ligand−Receptor Analysis Software

In addition to more conventional ligand-based methods, Core Hopping offers receptor-based scaffold hopping, exploiting information about the active site and known binding poses to guide the search for novel cores.

Details

Compounds can fail in drug development, or worse, commercially-available medications can be recalled due to unforeseen toxicity, selectivity, potency, and other unsuitable physicochemical properties. These issues can often be a function of undesirable core properties. Core hopping allows for the rapid screening of novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties while preserving key R-group interactions. In addition to lead optimization, core hopping can also be valuable in idea generation for novel derivatives to a known drug.

Schrodinger's Core Hopping program not only provides the traditional ligand-based methods for exploring different scaffolds, but also offers a receptor-based method that will accurately account for detailed ligand-receptor interactions of compounds containing novel cores.

Software Link : Core Hopping - Ligand−Receptor Analysis Software

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ToxExpress - Gene expression database

The foundation of Gene Logic's ToxExpress® Program is our ToxExpress® System. Developed in collaboration with major pharmaceutical companies, the ToxExpress® System is the largest database of its kind, comprised of over 14,000 individual vehicle and normal control and drug-treated animal tissue samples. A consortium of our customers stringently evaluates compound selection, study protocols, and in-life data, resulting in a consistent, robust database that serves as a premier reference source for both gene expression and related in-life toxicology data.

The ToxExpress® System is designed to help extensively characterize compounds, to facilitate the drug development process and aid in decision-making. The ToxExpress® System supports end-user research efforts and extensive knowledge building in four major areas:

• Investigative Toxicology
• Predictive Toxicology
• Mechanistic Toxicology
• Safety Biomarker Discovery 

Software Link: ToxExpress - Gene expression database 

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CombiGlide - Ligand−Receptor Analysis Software

CombiGlide combines accurate ligand-receptor scoring, clever combinatorial docking algorithms, and highly efficient core-hopping technology to design focused libraries and identify new scaffolds. These technologies greatly facilitate lead discovery and optimization efforts.

Details
The virtual chemical space that chemists are interested in is too large to be synthesized and screened, even using modern methods of combinatorial chemistry and robotic synthesis. Therefore, there is a real need for efficient and reliable methods to rationally select the optimal library members for synthesis. Additionally, once a promising lead compound is discovered, different core scaffolds as well as side-chain substitutions must be enumerated and examined to evaluate relative binding affinities towards a particular target. Accurate ligand-receptor scoring coupled with intelligent and efficient combinatorial docking and core-hopping methods can accelerate lead optimization and aid in designing the optimal, focused compound library for further synthesis.

Schrodinger's CombiGlide can flexibly vary the core or side-chain substitutions, creating virtual combinatorial libraries that may be screened for leads, identify novel scaffolds, or generate focused libraries in support of lead optimization efforts.

Software Link: CombiGlide - Ligand−Receptor Analysis Software

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DDDPlus - Drug design software

DDDPlus (Dose Disintegration and Dissolution Plus) is an advanced technology computer program that models and simulates the in vitro dissolution of active pharmaceutical ingredients (API) and formulation excipients dosed as powders, tablets, capsules, and swellable or non-swellable polymer matrices under various experimental conditions.

Details

DDDPlus (Dose Disintegration and Dissolution Plus) is an advanced technology computer program that models and simulates the in vitro dissolution of active pharmaceutical ingredients (API) and formulation excipients dosed as powders, tablets, capsules, and swellable or non-swellable polymer matrices under various experimental conditions.

Dissolution rate is a critical parameter of pharmaceutical dosage forms because the API needs to be dissolved before it can be absorbed. In vitro dissolution testing is important to screen formulations during development and to ensure batch-to-batch quality control during production. Throughout the world, more than 40 years of research have been devoted to characterizing the biopharmaceutical properties of drugs. Several guidelines have been published and all pharmacopoeias include a description of dissolution testing.

During drug development, in vitro dissolution testing is an important tool for evaluating candidate formulations and for understanding possible risks related to specific gastrointestinal factors, potential for dose dumping, food effects on bioavailability, and interaction with excipients. Today, dissolution studies are the most frequently used tools in the development, characterization, and utilization process of both immediate and controlled-release formulations.

Dissolution, in the simplest sense, can be defined as the sequence by which a solid solute enters into a solution in the presence of a solvent. We can define the dissolution rate as the amount of ingredient in a solid dosage form dissolved in unit time under particular conditions.

A DDDPlus simulation is essentially the numerical integration of a set of differential equations that coordinate well-characterized physical actions that occur during dissolution, including but not limited to changes in particle size distributions for both active and excipient ingredients, as well as changes in microclimate (surface) and medium bulk pH as formulation constituents dissolve.

DDDPlus allows you to select from one of 5 mathematical models and 5 dosage forms used to describe the dissolution of a single ingredient. The mathematical models for the in vitro dissolution simulation account for the effects of:

• Physicochemical properties of the formulation ingredients under study: pKa's, solubility, diffusion coefficient, and density.
• Manufacturing properties for immediate release dosage forms.
• Particle size distribution for each of the formulation ingredients.
• Different flow patterns and fluid velocities for each experimental apparatus.
• Interactions between the active ingredient and formulation excipients.
• Microclimate pH-dependence of solubility and dissolution/precipitation.
• Micelle-facilitated dissolution through the incorporation of surfactants in the media.
• In spite of its sophistication, DDDPlus is relatively easy for someone with a background in formulation and chemistry to learn and use. DDDPlus incorporates an intuitive and modern graphical user interface that enables rapid and smooth transition from setting up inputs to evaluating results.

Outputs are displayed with immediate on-screen text and graphics for single simulations, and can be saved to Microsoft Excel-compatible tab-delimited ASCII text files for both single and multiple simulations. Extended analyses through Parameter Sensitivity Analyses and Virtual Trials provide insight into the probable behaviors of formulations under varying conditions and can guide experimental efforts to focus precious resources where they will do the most good. 

 

Software Link: DDDPlus - Drug design software

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Liaison - Ligand−Receptor Analysis Software

Liaison applies linear interaction approximation to accurately compute binding affinities for series of ligands with similar binding modes, making it a powerful tool for lead optimization.
Details
Accurate ranking of binding affinities is crucial in the lead optimization phase of pharmaceutical research in order to develop potent, effective drug candidates. Both academic groups and the pharmaceutical industry have invested a great deal of effort to meet this challenge. Several approaches have been developed, ranging from rapid QSAR-based scoring functions to computationally intensive free energy perturbation (FEP) calculations. But none have fully met the needs of researcher and developers. QSAR-type approaches, though rapid, involve many approximations and produce large errors in binding energy predictions. FEP approaches are more accurate, but cannot be used when ligand structures vary significantly. They also incur substantial CPU costs.

Linear interaction approximation (LIA) is a way of combining molecular mechanics calculations with experimental data to build a model scoring function for the evaluation of ligand-protein binding free energies. LIA methods strike a perfect balance between accuracy and computational cost.

Software Link : Liaison - Ligand−Receptor Analysis Software

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Strand - Drug design software

Strand's new generation tool, Sarchitect, is meant for Quantitative Structure Activity Relationship (QSAR) studies and modeling of ADME / Tox properties. Sarchitect allows model builders to build best possible models of their data and equally importantly, monitor and improve the models over a period of usage.

Details

Modeling and predicting drug-relevant properties of molecules is a critical issue for scientists working in drug discovery research. Strand's new generation tool, Sarchitect, is meant for Quantitative Structure Activity Relationship (QSAR) studies and modeling of ADME / Tox properties. Sarchitect allows model builders to build best possible models of their data and equally importantly, monitor and improve the models over a period of usage. It allows users of the models to optimize complex multi-dimensional ADME/Tox properties of molecules while retaining their biological activity.

The Sarchitect platform empowers computational and medicinal chemists, modelers, DMPK scientists and other users with:

• QSAR modeling and deployment platform.
• Powerful algorithms, interactive views, single click model building, intuitive workflows for chemists and customized scripting.
• Ready to use predictive QSAR models for ADMET end points.
• Successful drugs, virtually now! 

Software Link: Strand - Drug design software

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Phase - Pharmacophore modeling software

Phase is a complete package of pharmacophore modeling tools that offers scientists an unparalleled level of control at each step. Fast, accurate, and highly configurable, Phase is a powerful tool for hit generation and lead hopping.

Details

As researchers continue to search for new targets of therapeutic interest, transmembrane and G-protein coupled receptors are of ever-increasing importance. However, crystal structures for these targets may be impossible to resolve, posing great challenges in rational drug design. Structure-based virtual screening is not an option when the active site geometry is unknown, but assaying an entire library for hits is an inefficient and expensive proposition.

Pharmacophore modeling solves this problem by determining the spatial arrangement of chemical features that confer drug activity toward a target receptor. Having established the chemical space occupied by active ligands, pharmacophore modeling software allows researchers to create 3D structure-activity relationships, screen databases, and generate hits without the benefit of a receptor structure. 

 

Software Link : Phase - Pharmacophore modeling software

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QikProp - Drug design software

QikProp efficiently evaluates pharmaceutically relevant properties for over half a million compounds per hour, making it an indispensable lead generation and lead optimization tool.

Details

Nearly 40% of drug candidates fail in clinical trials due to poor ADME (absorption, distribution, metabolism, and excretion) properties. These late-stage failures contribute significantly to the rapidly escalating cost of new drug development. The ability to detect problematic candidates early can dramatically reduce the amount of wasted time and resources, and streamline the overall development process.

Accurate prediction of ADME properties prior to expensive experimental procedures, such as HTS, can eliminate unnecessary testing on compounds that will ultimately fail; ADME prediction can also be used to focus lead optimization efforts to enhance the desired properties of a given compound. Finally, incorporating ADME predictions as a part of the development process can generate lead compounds that are more likely to exhibit satisfactory ADME performances during clinical trials. 

 

Software Link : QikProp - Drug design software

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ConfGen - Ligand−Receptor Analysis Software

Reproducing bioactive ligand geometries in minimally sized conformer sets, accurate results from high-performance ConfGen calculations save time and effort in downstream applications.

Details
Conformer generation is useful in many aspects of both molecular modeling in general and drug discovery in particular. The relative energies of small molecule conformations play a crucial role in determining shape, function, and activity. Moreover, the ability to generate a bioactive conformer is a vital pre-requisite to any successful computer-aided drug design project.

While it's impossible for a conformer search algorithm to determine a flexible ligand's bioactive conformer with absolute confidence, carefully considered search criteria do allow an algorithm to reject conformers likely to be high energy or inactive. Beyond merely expediting the conformer search process, this approach creates efficiently sized conformer sets that nevertheless contain a reasonable approximation of the bioactive geometry.

Efficient conformer sets have wide-ranging ramifications in downstream applications. For example, with fewer irrelevant conformations to process, virtual database screens and shape-based similarity searches run to completion in a fraction of the time without sacrificing accuracy.

Software Link: ConfGen - Ligand−Receptor Analysis Software

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QSite - Drug design software

QSite applies quantum mechanics to the reactive center of a protein active site and molecular mechanics to the rest of the system. Its accuracy allows detailed understanding of reactions involving proteins, making it a powerful tool for lead optimization.

Details
Insight into reactive chemistry is crucial to understanding the mechanism of drug receptor interactions in systems where the ligand is covalently bound to the receptor. For example, it's necessary to study the transition states between bound and unbound forms in order to design antibiotics that are not subject to inactivation by beta lactamases. Classical molecular mechanics (MM) methods cannot describe the electronic changes during a reaction, and are ill-equipped to address ligand-receptor interactions in systems containing metals.

Ab initio quantum mechanics (QM) is required to study reactive chemistry or interactions involving transition metals in a protein environment. However, even with today's computer technology, full QM calculations of entire proteins are still intractable.

Mixed QM/MM calculations provide the ideal solution by separating out the reactive core, which can be accurately described with QM, while treating the remainder of the complex more efficiently with MM. While QM/MM may not be needed for every structure-based drug design project, many important systems cannot be effectively addressed by any other computational means. QM/MM is therefore a key component in the arsenal of computational drug discovery.

Software Link : QSite - Drug design software

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Screen Suite - Virtual screening technology in Biology

Screening toolkit for compound libraries using molecular descriptors

Details

Screen Suite: Components of the virtual screening technology

Ligand-based screening of large molecular databases has become an invaluable tool in early phase drug-discovery. The Screen Suite is a ligand-based high throughput virtual screening package that provides powerful tools for chemical (2D) and shape (3D) similarity searches of large molecular libraries. Screen provides several different fingerprints sets, such as the ChemAxon chemical fingerprint, pharmacophore fingerprint and ECFP/FCFP as well as several dissimilarity metrics and metrics optimization that can be used to tune your processes to achieve optimal search results.

The Screen Suite is available commercially as 2D Descriptor package, Screen2D (includes the ChemAxon Chemical Fingerprint) and Screen3D. All components of the Screen Suite are accessible as command line applications, and also include a full Java and .NET based Application Programming Interface (API) through which they can be integrated into existing in-house or commercial third party applications.

Descriptor package in Screen

Flexible descriptor accessibility
The Screen2D Descriptor package contains fingerprint generators for chemical structures, pharmacophores, extended connectivity (ECFP) and functional class (FCFP) descriptors and can be used to generate and tune fingerprints for use in any screening process. Descriptor generation is also supported through ChemAxon's Chemical Terms scripting language, to let create complex fingerprints which consider single or combined molecular attributes that can be based on topological or physicochemical properties e.g. partition coefficients, hydrogen bonding donor-acceptor accessibility or acidic properties.


Diverse fingerprints for different purposes

BCUT
The BCUT descriptors are based on a special matrix representation of the connectivity table of the molecules extended with certain physical and physicochemical atomic properties and are capable of encoding compound properties relevant to intermolecular interactions. ChemAxon's BCUT descriptor encodes atom charge polarizability and hydrogen bonding donor-acceptor properties. The BCUT descriptors are widely used in diversity analyses and QSAR applications.

Chemical Fingerprint
The chemical fingerprint is a path-based bit-string descriptor containing certain limited information on the molecular structure. The chemical fingerprint can be used in database handling for structural searches (e.g. substructure and full structure searching) and for similarity searches. It also can be used for the diversity analysis of compound libraries.

Pharmacophore Fingerprint
The pharmacophore fingerprints are atom-based fingerprints designed to characterize the compounds' binding related structural and physicochemical properties. Pharmacophoric features include all those binding related structural or physicochemical properties of chemical compounds that are thought to be responsible for pharmacological activity. Chemical attributes taken into account usually include hydrogen bond donor/acceptor capability, charge, hydrophobicity and aromaticity. The fingerprint generation is based on simple statistics determined by the relative arrangement according to topological distances of pharmacophore points, which results in the two dimensional nature of the fingerprint.

ECFP/FCFP
The Screen 5.4 Suite supports the use of circular fingerprints in the screening process. In contrast to path-based fingerprints ECFP/FCFP are not suitable for substructure search, but are relevant for full structure and similarity searches. For similarity searches circular fingerprints are known to yield more consistent results than path-based descriptors. The use of the FCFP gives researchers the freedom to include arbitrary physical, physicochemical or any arbitrary data in the fingerprint itself. Calculation of these properties can be supported by the Chemical Terms language.


Screen2D

Screen2D is a ligand-based virtual high throughput screening platform, that can be used to carry out similarity searches on large molecular databases using different descriptors and several different metrics to quantify dissimilarity of compounds. Screen functionality is available through API and command line, via Pipeline Pilot and KNIME connectors, and some features are implemented within Instant JChem and JChem for Excel desktop applications.

High speed
The screening process is fast, with up to 100,000 compounds per second being screened on a single desktop PC.

Great flexibility in descriptor usage
Screen's 2D descriptor package includes many descriptors, such as BCUT, Chemical and Pharmacophore fingerprints and ECFP/FCFP. Besides the extendibility of the FCFP by user defined additional parameters, researchers can use arbitrary sets of scalars (i.e. physicochemical properties) as descriptors or any in-house generated fingerprints. Screen's modularity allows for the user to use their own well established and validated descriptor sets.

Versatile metrics
Screen2D comes with a set of metrics to measure dissimilarity between compounds. It supports the Euclidean, Tanimoto and Tversky metrics and also modified versions, such as the Dice metrics. Screen2D also supports metrics optimization - by selecting appropriate training sets, the optimization step increases enrichment significantly, giving smaller, more focused hit sets.


Screen3D

In addition to topology based screening, the Screen Suite includes 3D shape similarity based searching using Screen3D. Screen3D introduces a novel flexible alignment technique, which provides reasonable alternative hit results as compared to previous 3D screen engines. Screen3D is also available both through the API and as a command line program.

High speed 3D shape similarity searching
A key feature of Screen3D is its high speed. Currently Screen3D is ten times faster than any alternative approach which, besides the novel alignment algorithm is achieved by introducing a preprocessing step carried out separately from the actual screening process. Screen3D also compares very well in providing better enrichment in the first 1% of the hits than most alternative software. Screen3D's scalability makes it suitable to search in very large molecular databases.

Multiple 3D screening strategies
Screen3D can be used to carry out different shape similarity searches. Beyond fully flexible matching Screen3D can align flexible database compounds to rigid query molecules (rigid-flexible), or alternatively to align rigid database compounds to rigid query molecules (rigid-rigid) using on-the-fly generated conformation ensembles.

Two types of 3D similarity screening methods are available in Screen3D: Shape" and "Match". Due to their dissimilar methodologies these approaches capture different aspects of binding. While "Shape" evaluates full molecular shape similarity measures that can model ligand binding to a protein's active site 

Software Link: Screen Suite - Virtual screening technology software Biology

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