Intelligent Pharma
Molecular Modeling Services

Services

Intelligent Pharma offers a variety of services in computationally aided drug discovery. Using our computational chemistry expertise, our molecular modeling department can help your team design and develop new drugs. Our specialists use Intelligent Pharma’s own technology as well as 3rd party software.

Our cutting-edge technologies are amongst the best in the computational chemistry field, and we are constantly developing new technology to meet the ever-changing needs of the market. With our technology and team of skilled, experienced scientists, we can assure the highest quality services.

  • Allosteric Binders

    OBJECTIVE

    To discover molecules that bind to an allosteric site of a protein.

     

    PROJECT

    An allosteric site can regulate the function of a protein, making them very interesting for drug discovery. They also have a low conservation amongst proteins, allowing for the development of highly specific drugs. Currently, few marketed drugs use allosteric regulation of the target to achieve their function, which could be due to the difficulty in detecting them.

    Using our technology HYPERION, allosteric sites of your protein targets can be determined. HYPERION detects ligand binding sites, considers their 3D structural arrangements and conservation, and then evaluates them by normal mode analysis to determine allosteric sites. Druggability is assessed next using molecular dynamics simulations. SELENE, a technology that simulates the interaction of small molecules and proteins, can then determine potential small molecular binders. Finally, the most promising scaffolds are found through a clusterization of the best molecules using PEGASUS.

     

    COMPETITIVE ADVANTAGE

    • Allosteric sites on various proteins can be determined rapidly.
    • Druggability studies evaluate which proteins have the best potential for the development of a good binder/hit.
    • SELENE is a high throughput docking tool that can simulate the interaction of many molecules with an allosteric site in a short time.
    • Determination of different molecular families that can bind the protein allosterically increases the success of the project.

    The orange sphere indicates the allosteric binding site on L-lactate dehydrogenase, which was correctly predicted by HYPERION

  • Determination of mechanisms of action

    OBJECTIVE

    To determine the mechanism of action of your molecule

     

    PROJECT

    The most promising molecular targets are determined using structure based similarity searches and ligand-target experimental binding energies; however, specific targets can be prioritized according to your findings. The best targets are then further analyzed using two different technologies. Based on docking, SELENE simulates the interaction of a molecule with a protein or DNA. Based on molecular interaction field analysis, HERCULES compares the 3D molecular fields of your molecules of interest and other active compounds.

     

    COMPETITIVE ADVANTAGE

    • This process uses both experimental data and structural information about the targets and molecular binders.
    • Manual intervention allows for the inclusion of  your own findings.
    • New receptors and indications are determined for your molecule.

  • Determination of new inhibitors

    OBJECTIVE

    To identify new inhibitors for a specific target

     

    PROJECT

    Using SELENE, our receptor based virtual screening tool, and the 3D structure of your target, we can determine new inhibitors from any of our databases or from your own. Specific molecular databases can also be created for your project.

    If there is no determined 3D structure for your target, but enough data exits, our specialists can make a homology or ab-initio model of your target. If necessary, binding sites on proteins can be tracked. If no structure can be created, inhibitors can be determined using ligand-based virtual screening as explained in Hit Identification.

    If there are known inhibitors for your target, they can be used to optimize the screening protocol. We can use molecular dynamics and high throughput docking to determine the conformation of your target that can best recover active compounds. The scoring function of SELENE can also be optimized by internal technology. 

     

    COMPETITIVE ADVANTAGE

    • All relevant experimental information, such as biological targets and known molecular binders, are used to obtain the best results. 
    • High speed molecular dynamics simulations running on GPU’s.
    • The following constructed models can be taken advantage of in the optimization of your inhibitors to Lead compounds.
  • Hit identification

    OBJECTIVE

    To identify new compounds with a specific activity

     

    PROJECT

    HERCULES, PEGASUS, and SELENE, our 2D, 3D, and receptor-based virtual screening tools, are used in combination with a customized database of molecules to screen for new hits.  We have many databases at our disposal, including those consisting of natural compounds, commercial compounds, drug-like compounds, small molecules, peptides, etc.

    Some of the most common tasks for this project include determining the bioactive conformation of active molecules and preparing biological targets. 3D molecular field comparisons, docking methods, and structure based ligand comparisons are used to identify potentially active compounds. If enough active and inactive molecules are initially known, a pharmacophore model may be better suited. The detected compounds are then sorted into families to facilitate the choice of the compounds subjected to synthesis and biological screening.

    COMPETITIVE ADVANTAGE

    • The structure of the receptor target does not have to be known.
    • Our computational approaches are designed for scaffold hopping.
    • We can model the structure of the receptor (see Determination of inhibitors)
    • Our databases of compounds are readily available and can be used to create a project-specific databases.

     

  • Hit to Lead

    OBJECTIVE                                   

    To improve the activity and other pharmacological properties of a molecular family

     

    PROJECT

    Different computational approaches are used to optimize properties of a molecular family. The approach used depends on the available experimental data as well as other information, such as the receptor structure. Usually, a predictive model is built for different types of activities and pharmacological properties by using methods like MEDEA, our QSAR and SAR platform.

    The obtained Structure Activity Relationship (SAR) rules can be complimented with structural information from the target and ligand, which is generated using SELENE. These rules can be then used by medicinal chemists for the design of structurally new molecules. Quantitative SAR (QSAR) is used to find the best molecules out of the large virtual set just created. At Intelligent Pharma, we test a variety of approaches (1D to 3D QSAR, pharmacore based, SVD, PLS, etc.) to select the best method for measuring each property. Eventually, a small set of new and improved molecules is obtained for synthesis and testing. 

    CHIRON is a tool based on a genetic algorithm which helps us to choose the best compounds in a hit to lead process for synthesizing and testing. More information about CHIRON is available at http://www.intelligentpharma.com/tools.php

     

    Competitive Advantage

    • Our computational chemists and mathematicians work directly with your research teams.
    • Depending on circumstances, a variety of our in-house tools can be applied to each project.

    • MEDEA allows for the building and selection of the best QSAR model.
    • Fragment databases allow for a generation of structurally new molecules.
    • The protocol can be used in further rounds of optimization.
    • Computational approaches allow you to minimize synthesis efforts, in vitro testing, and time spent on drug discovery. 

  • ADME/Tox prediction

    OBJECTIVE

    To perform ADME and toxicology predictions to help select molecules for synthesis and testing

     

    PROJECT

    In order to choose molecules with the most favorable characteristics, ADME properties can be predicted for large groups of molecules. We can determine molecular characteristics such as the number of hydrogen bond donors and acceptors, the number of flexible bonds, molecular weight, polar surface area and volume, the number of nitrogen bonds, overall charge, and pKi.

    We have developed models to predict properties early in the drug discovery process, such as cardiovascular toxicity (hERG), solubility (logS), and Blood Brain Barrier penetration. Using MEDEA, our QSAR and data mining technology, our models can be optimized for your molecules. This allows you to specifically select a small number of molecules for synthesis and experimental testing. 

     

    COMPETITIVE ADVANTAGE

    • Already prepared models can be applied directly.
    • Models can be optimized for your type of molecule.
    • New models to predict other properties can be prepared using our technology platform.

  • Lead optimization

    OBJECTIVE

    To enhance the most promising compounds in order to improve effectiveness, reduce toxicity and/or increase absorption. A similar strategy described in Hit to Lead is followed.

     

  • Drug Reprofiling

    OBJECTIVE

    • To find new indications for your drug
    • To determine other drugs with your indication of interest

    PROJECT

    HERCULES, our ligand based virtual screening tool, is used to determine molecules with similar molecular fields. Comparable molecular fields generally behave similarly within the cell. Those compounds can then be screened against a target of interest using SELENE. Molecules with high scores from both tools are inspected visually to select the most promising indication for your drug or other drugs with the indication of interest.

    To find new indications for a drug, PYTHIA is used. Protein targets are predicted for the drug, and a target profile is created. By comparing the target profile to those in our databases, the most promising indication can be found. The most important targets are also obtained, which helps with the designing of experiments to reposition the drug. 

     

    COMPTETITIVE ADVANTAGE

    • We  have participated in successful drug re-profiling projects.
    • We use information on biological targets and molecule binders. 
    • Indications are predicted based on experimental data.

     

  • Selectivity studies

    OBJECTIVE

    To determine and improve the selectivity of your compounds

     

    PROJECT

    If a molecule is prone to binding  to targets other than the desired target, structural differences can be taken advantage of to design more selective molecules. The 3D make-up of the protein binding site and the structure of the known small molecule or protein binder are used to achieve this. This information can then be used in our high throughput screening tools.

    HERCULES compares molecular fields amongst molecules and will disfavor specific regions or fields around the reference molecule that are known to promote off-target binding.

     SELENE allows us to simulate the interactions between targets and thousands of compounds. We can then determine the most selective and active compounds by analyzing the binding energy and position of each compound with respect to the desired and undesired targets.

    Using MEDEA, we can construct pharmacore models, taking into account positive and negative contributions of physio-chemical properties in 3D space. We can then scan large libraries of molecules to determine specific binders for your target.

    Selectivity can also be achieved using allosteric inhibitors (See Determination of Allosteric Inhibitors).

     

    COMPETITIVE ADVANTAGE

    • We use information on biological targets and their molecule binders.
    • Access to a broad selection of tools and protocols allow us to tailor our approach towards your specific project circumstances.
    • Large databases can be screened in a short amount of time.
    • We can help in the design of new derivatives of your compounds.
  • Extraction of biological and chemical patterns

    OBJECTIVE

    To extract patterns from your compounds in order to understand and rationalize its behavior. This information is usually then used for drug design.

  • Identification of more synthesizable or scalable compounds

    OBJECTIVE

    To identify if the analogues of your compounds with different scaffolds are easily synthesizable or scalable

  • Extension of patents

    OBJECTIVE

    To determine non-structural analogues of your compounds to potentially include in a patent

     

  • Determination & selection of back-ups

    OBJECTIVE

    To determine the most promising compound amongst your lead compounds

  • Crystal Engineering

    OBJECTIVE

    To determine excipients and molecules for co-crystallization of your drug