BIOVIA DISCOVERY STUDIO 2022 cracked suite

BIOVIA DISCOVERY STUDIO 2022 cracked suite

$ 150.00

BIOVIA modeling and simulation software allows scientists to perform computations of chemical, biological and materials properties; to simulate, visualize and analyze chemical and biological systems; and to communicate the results to other scientists. Scientists can investigate and test hypotheses in silico prior to costly experimentation, reducing the time and expense involved in bringing products to market.

BIOVIA Discovery Studio life science modeling and simulation application supports in silico target identification and lead optimization using a wealth of trusted life science modeling and simulation methods.

The industry-leading BIOVIA scientific software portfolio integrates the diversity of science, experimental processes and information requirements. It connects people, processes and data end-to-end, across research, development, QA/QC and manufacturing.

Capabilities include Scientific Informatics, Molecular Modeling & Simulation, Data Science, Laboratory Informatics, Formulation Design, BioPharma Quality & Compliance and Manufacturing Analytics

Category: Tags: ,

Description

Biovia Discovery Studio

COMPREHENSIVE PREDICTIVE SCIENCE FOR THE LIFE SCIENCES

Comprehensive Modeling & Simulation for the Life Sciences

Today’s biopharmaceutical industry is marked by complexity: growing market demands for improved specificity and safety, novel treatment classes and more intricate mechanisms of disease. Keeping up with this complexity requires a deeper understanding of therapeutic behavior.

Modeling and simulation methods provide a unique means to explore biological and physicochemical processes down to the atomic level. This can guide physical experimentation, accelerating the discovery and development process.

BIOVIA Discovery Studio brings together over 30 years of peer-reviewed research and world-class in silico techniques such as molecular mechanics, free energy calculations, biotherapeutics developability and more into a common environment. It provides researchers with a complete toolset to explore the nuances of protein chemistry and catalyze discovery of small and large molecule therapeutics from Target ID to Lead Optimization.

With Discovery Studio you can:

  • Investigate and test hypotheses in silico prior to costly experimental implementation, thus reducing the time and expense involved in bringing products to market
  • Drive scientific exploration from target identification to lead optimization with a wealth of trusted life science modeling and simulation tools
  • Leverage BIOVIA Pipeline Pilot to automate processes, create and deploy custom workflows, and integrate data types, databases, and third-party or in-house tools
  • Enhance personal productivity and boost team collaboration by enabling researchers to share data and make better informed decisions

Simulations

INCLUDES THE HIGHLY VERSATILE CHARMm MOLECULAR MECHANICS SIMULATION PROGRAM

Biomolecular processes rely on a variety of dynamic interactions between proteins, ligands, solvents and ions. Often, the specifics of these interactions are difficult to capture via physical experimentation alone due to the short time scales over which they occur. Simulation can help elucidate the energetics of these processes, providing insight into their mechanism of action and properties.

Discovery Studio utilizes the highly versatile CHARMm molecular simulation program. With over 30 years of peer-reviewed academic research, CHARMm targets the study of biological systems such as proteins, peptides, small molecule ligands, nucleic acids, lipids and carbohydrates.

https://youtu.be/-6f7cn6vM-M?si=dbqrM5_l5NID4NRJ

Simulate

  • CHARMm
    • Perform explicit solvent or implicit solvent-based minimizations and Molecular Dynamics (MD) simulations
    • GPU-enabled via DOMDEC and OpenMM
  • NAMD
    • Perform explicit solvent MD simulations
    • Solvate a protein with explicit membrane and run MD simulations
  • DMol3 / CHARMm
    • Calculate single point energies or perform minimizations of receptor-ligand complexes using hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) simulations

Model

  • Support for a broad range of force fields, including CGenFF, charmm36, CHARMm and more
  • MATCH method for typing ligands with charmm36
  • Full support of CHARMM patching mechanism
  • Fast explicit aqueous solvation method with optional counter-ions suitable for very large molecular systems
  • Solvation of transmembrane protein into pre-equilibrated lipid bilayer
  • Analysis of MD trajectories

Explore

  • Perform quick and accurate protein ionization and residue pKs predictions for protein preparation
  • Use CDOCKER, a CHARMm-based docking engine to perform flexible ligand-based docking and refinement
  • Perform pose optimization of multiple ligands in the context of a receptor
  • Calculate binding energies of docked poses
  • Accurately predict relative ligand binding energy for a congeneric ligand series using the free energy perturbation (FEP) method
  • Calculate the relative free energy of binding for a combinatorial library of ligands modeled by Multi-Site Lambda Dynamics (MSLD)
  • Estimate ligand binding free energy and study ligand unbinding using CHARMm-based Steered Molecular Dynamics (SMD) simulations
  • Examine electrostatic potential effects with CHARMm Poisson-Boltzmann (PB) equation

Macromolecule Design and Analysis

DELIVERS A COMPREHENSIVE PORTFOLIO OF VALIDATED SCIENTIFIC TOOLS TO ASSIST EVERY ASPECT OF MACROMOLECULE-BASED RESEARCH

Determining the three-dimensional structure and properties of macromolecules, such as enzymes and antibodies, is a fundamental component to a wide range of research activities. For example, different conformations which arise from normal molecular dynamics or interactions with ligands or other proteins may reveal novel binding sites or provide clues as to its function.

While thousands of molecules have had their structures resolved experimentally, obtaining high fidelity structural data remains a nontrivial process.

Simulation can augment physical experimentation by providing insight into macromolecular structure. Additionally, techniques such as homology modeling can help predict structural models for novel molecules, guiding therapeutic design and protein engineering efforts.
Discovery Studio delivers a comprehensive portfolio of market leading, validated scientific tools, able to assist in every aspect of macromolecule-based research.

Search

  • Perform multiple sequence searches using BLAST and PSI-BLAST against local or NCBI databases
  • For multiple chain proteins, simultaneously and independently perform multiple sequence alignments of each protein chain
  • Predict the transmembrane helices in transmembrane protein sequences
  • Predict sites prone to Post Translational Modifications (PTMs) using sequence-based motif searching

Model

  • Analyze and prepare structures from 3D structure repositories (e.g., PDB)
  • Generate 3D structure models using MODELER
  • Verify the quality of a structure model
  • Use LOOPER to systematically search loop conformations and rank using CHARMm
  • Graft loop conformations from a template structure onto a target model
  • Systematically optimize amino acid side-chains using ChiRotor CHARMm simulations
  • Use ZDOCK to perform protein-protein docking and examine binding partner interactions
  • Study conformational flexibility with explicit solvent-based Molecular Dynamics (MD) simulations using CHARMm or NAMD

Design

  • Predict electrical properties of the protein, including pH-dependent stability and protonation states and the isoelectric point
  • Conduct thermal or pH-based mutational stability and binding affinity predictions
  • Identify potential stable disulfide bridge locations
  • Calculate biophysical properties important for protein formulation, including viscosity and solubility

Structure-Based Design

SUPPORTS PHARMACEUTICAL R&D FROM HIT DISCOVERY THROUGH TO LATE-STAGE LEAD OPTIMIZATION

Structure-Based Design (SBD) and the related Fragment-Based Design (FBD) are well established strategies in the rational development of small molecule drugs. Knowledge of how a small molecule binds into a protein affords considerable advantages, both in terms of prioritizing compounds for early stage screening, through to optimizing potency and selectivity. Discovery Studio delivers a comprehensive, scalable portfolio of scientific tools, tailored to support and assist SBD and FBD strategies from hit discovery through to late-stage lead optimization.

Prepare

  • Analyze and prepare 3D structures (e.g., PDB, X-ray structure, homology model) for SBD
  • Automatically build neighboring molecules based on crystal packing and analyze their interactions
  • Predict residue ionization states at chosen pH
  • Identify and study putative ligand binding sites
  • Prepare ligands with extensive set of characteristics and calculate 3D coordinates
  • Generate ligand conformations
  • Filter ligands based on drug-likeness, molecular properties, or to remove undesirable groups or features

Screen

  • Hit Identification and optimization
  • Perform virtual screening on ligands and fragments using either the CATALYST pharmacophore engine, or the LibDock or CDOCKER docking approaches
  • Perform docking with GOLD §
  • Perform in situ lead optimization using classical medicinal chemistry reaction transformations and commercially-available reagents
  • Scaffold-hop or perform R-group substitutions in situ using molecular fragments derived from commercially-available compounds

Score

  • Calculate binding energies with MM-PBSA or MM-GBSA CHARMm-based methods
  • Accurately predict relative ligand binding energy for a congeneric ligand series using the free energy perturbation (FEP) method
  • Calculate the relative free energy of binding for a combinatorial library of ligands modeled by Multi-Site Lambda Dynamics (MSLD)
  • Identify critical interacting residues using a comprehensive set of favorable, unfavorable and unsatisfied non-bond monitors
  • Profile and prioritize screening hits, optimizing potency and target specificity

Extend

  • Design and optimize combinatorial libraries as new starting points for further screening.
  • Combine your scores with classical QSAR, fingerprints, and Quantum Mechanics based descriptors and create advanced predictive models
  • Minimize toxicity using TOPKAT and optimize the pharmacokinetic profile.

Ligand- and Pharmacophore-based Design

ASSIST IN DE NOVO DRUG DESIGN, MULTI-TARGET DRUG DESIGN AND ACTIVITY PROFILING

The binding interactions of proteins and ligands arise from a variety of steric and electrochemical factors. Understanding these interactions can help researchers more rapidly identify promising new therapeutic candidates.

Pharmacophores map these features in 3D space, providing a simple means to screen libraries of compounds virtually, characterize the binding of existing leads and optimize their performance.

BIOVIA Discovery Studio utilizes the CATALYST Pharmacophore Modeling and Analysis toolset to assist in the assessment of small molecule therapeutics with or without target-structured data. It supports de novo drug design, multi-target drug design and activity profiling to drive small molecule R&D.

https://youtu.be/tZIC1FIvnm8?si=xn2gnh0n2mwfZHAz

Build

  • Automatically generate pharmacophores from the data available
    • Sets of active ligands
    • Receptor binding sites
    • Receptor-ligand complexes
  • Perform rigorous Pharmacophore validation based on sets of control compounds with known activity.
  • Hypotheses can include
    • Geometric, feature-based queries
    • Shape-similarity
    • “Forbidden” space
  • Go beyond the limitations of classical pharmacophore elucidation algorithms by exploring Ensemble Pharmacophores for very large/diverse compound sets with a risk of multiple modes of action

Apply

Conduct robust Pharmacophore screening studies

  • Build and search databases of 3D conformations
  • Consider and analyze the full conformational space of your ligands
  • Explore off-target activity and drug repurposing using the PharmaDB* database

Discovery Studio now includes the most extensive reported database for ligand profiling. Built from, and validated using, the scPDB*, the PharmaDB contains approximately 240,000 receptor-ligand pharmacophore models.

Design

Design and characterize your ligands and combinatorial libraries

  • Enumerate reaction- or core-based libraries
  • Enumerate ionization states, tautomers and isomers
  • Filter poor candidates with undesirable functional groups and Lipinski and Veber rules or your own criteria
  • Calculate numerous physicochemical and fingerprint properties
  • Optimize combinatorial libraries using Pareto optimization, diversity and similarity analysis
  • Clustering tools and 3D visualization using PCA analysis

QSAR, ADMET and Predictive Toxicology

ASSESS THE POTENTIAL RISK POSED BY UNFAVORABLE PHARMACOKINETIC PROPERTIES AND POTENTIAL TOXICITY

Understanding and quantifying structure-activity relationships can significantly impact lead optimization and drug development by minimizing tedious and costly experimentation.

Build, validate and apply your own models based on a wide range of approaches, and keep improving them as new data become available.

Assess the potential risk posed by unfavorable pharmacokinetic properties and potential toxicity using BIOVIA’s distributed models, extend them to better cover your proprietary chemical space and use the comprehensible indications to navigate around such liabilities.

QSAR

  • Comprehensive and consistent data preparation:
    • Ligands: remove duplicates and handle tautomers and ionization
    • Prepare response property (scaling and binning)
    • Split your data into training and test sets with the appropriate methods
  • Choose from a large number of physicochemical, topological, electronic, geometric. fingerprint and Quantum Mechanics based descriptors
  • Create statistical models including Bayesian, MLR (Multiple Linear Regression), PLS (Partial Least Squares), and GFA (Genetic Functional Analysis)
  • Analyze and validate models using model applicability domains (MAD), automatic test set validation, cross validation and statistical metrics
  • Identify Matched Molecular Pairs (MMPs) transformations and study activity cliffs

ADMET

Get an early assessment of your compounds by calculating the predicted ADMET (absorption, distribution, metabolism, excretion and toxicity) properties for collections of molecules such as synthesis candidates, vendor libraries, and screening collections. Use the results to eliminate compounds with unfavorable ADMET characteristics and evaluate proposed structural refinements, designed to improve these properties prior to synthesis.
ADMET descriptors include:

  • Human intestinal absorption
  • Aqueous solubility
  • Blood brain barrier penetration
  • Plasma protein binding
  • CYP2D6 binding
  • Hepatotoxicity
  • Filter sets of small molecules for undesirable function groups based on published SMARTS rules

Toxicity

Evaluate your compounds’ performance in experimental assays and animal models. Compute and validate assessments of the toxic and environmental effects of chemicals solely from their molecular structure. TOPKAT® (TOxicity Prediction by Komputer Assisted Technology) employs robust and cross-validated Quantitative Structure Toxicity Relationship (QSTR) models for assessing various endpoints and utilizing the patented Optimal Predictive Space validation method to assist in interpreting the results.

Please note:
Details on our extensible TopKat models have been published in QSAR Model Report Format (QMRF) on the European Commission Joint Research Center (JRC)’s “QSAR Model Database”*.

  • Ames mutagenicity
  • Rodent carcinogenicity (NTP and FDA data)
  • Weight of evidence carcinogenicity
  • Carcinogenic potency TD50
  • Developmental toxicity potential
  • Rat oral LD50
  • Rat maximum tolerated dose
  • Rat inhalation toxicity LC50
  • Rat chronic LOAEL
  • Skin irritancy and sensitization
  • Eye irritancy
  • Aerobic biodegradability
  • Fathead minnow LC50
  • Daphnia magna EC50

Antibody Modeling

BIOTHERAPEUTICS AND ANTIBODY MODELING

Biotherapeutics offer a range of unique benefits over small molecule drugs. Their increased affinity and selectivity have allowed researchers to address new and difficult targets.

This has led to a dramatic increase in R&D projects centered on antibodies and other biological modalities for treatment such as bispecifics. However, these projects must also overcome similar challenges in safety and pharmacokinetics faced by small molecules, albeit from a different perspective. Factors such as high immunogenicity or low solubility can kill development on an otherwise effective candidate.

Modeling and simulation can significantly advance the development of these new classes of therapeutics. For example, researchers can predict an antibody’s formulation properties and suggest mutations to improve them rapidly and at low cost compared to laboratory experimentation alone.

To this end, BIOVIA Discovery Studio offers a rich set of tools to help guide the design of biotherapeutics, allowing teams to optimize the performance of candidates in silico and streamlining their physical work.

Model

  • Automated modeling cascade to easily and rapidly generate high quality 3D antibody full-length, Fab or Fv models from a set of light and heavy antibody chain sequences and a curated PDB antibody template database
  • Full support for commonly used antibody annotation schemes –  IMGT, Chothia, Kabat and Honegger
  • Simultaneously and independently perform multiple sequence alignments of heavy and light chains
  • Additional expert tools to identify antibody template structures and build high quality homology models
  • Ability to build bispecific full length antibody structures
  • Refine CDR loops using either template, loop grafting or de novo loop modeling
  • Perform detailed model analysis

Design

  • Conduct thermal or pH-based mutational stability and binding affinity predictions
  • Identify potential stable disulfide bridge locations
  • Perform antibody-antigen docking using ZDOCK to identify critical interacting residues
    • Predict residue mutations for antibody humanization without compromising antibody stability or efficacy
    • Study conformational flexibility with explicit solvent-based Molecular Dynamics (MD) simulations using CHARMm or NAMD

Predict

  • Calculate biophysical properties including isoelectric point, solubility, viscosity (SCM*) and aggregation propensity (Developability Index – SAP*) for early stage assessment of suitability for development
  • Predict sites prone to Post Translational Modifications (PTMs) using sequence-based motif searching

Visualization

A FREE, FEATURE-RICH MOLECULAR MODELING APPLICATION FOR VIEWING, SHARING AND ANALYZING PROTEIN AND SMALL MOLECULE DATA

Molecular visualization is a key aspect of the analysis and communication of modeling studies. It enables a mechanistic understanding of a molecule’s structure to be visualized, so that key insights can be shared between computational modeling experts and collaborating team members.

The BIOVIA Discovery Studio Visualizer is a free, feature-rich molecular modeling application for viewing, sharing and analyzing protein and small molecule data. Experts and their colleagues can seamlessly and efficiently exchange results, without loss of either time or scientific information.

Visualize

  • Visualize and examine very large macromolecule systems (E.g., Ribosomes) using a wide range of display types
  • Support a range of stereo graphical options (E.g., split screen, hardware stereo)
  • Hardware graphics acceleration support for advanced visualization options such as depth cueing, blur and shading capabilities

Explore

Molecular graphics are not the only results that you might want to share. Other visualization capabilities include:

  • Sequences, including Chain view support for multi-domain proteins (E.g., Antibodies)
  • 2D and 3D Charting, Histograms, Heat maps and Data tables
  • Map interactions using a comprehensive set of favorable, unfavorable and unsatisfied non-bond monitors
  • Interactivity between multiple graphical views on the same data

Collaborate

Visualization is more than just about creating a graphical scene; its goal is to communicate and collaborate. With Discovery Studio products you can collaborate with colleagues using Storyboards to:

  • Capture, navigate, animate and share multiple views of structures
  • Incorporate scene transition, timing and auto-play features

Visualize Your Science

The Discovery Studio Visualizer provides a comprehensive collection of features to capture the specific nuances of your research:

General

  • High quality graphics with advanced display options and stereo support
  • Ability to generate publication quality images
  • Interactive 3D graphical view with associated hierarchy and data table views
  • Multiple sided surfaces and isosurfaces for enhanced molecular visualization
  • Ability to plot data from multiple data series with line and point plots, 3D plots and bar charts
  • Charting capability including heat maps, histograms, hit rate plots and more
  • Storyboard functionality to capture series of molecular views to demonstrate and share
  • Export storyboards as movies
  • Sorting, filtering and grouping functionality available for properties in the data table
  • Perl scripting to automate repetitive tasks or link tasks together for ease of use
  • Tool panels, tool bars and interface layout can be customized as desired
  • Support for a wide variety of structure and sequence file formats
  • RMS calculations available at different levels of detail
  • Monitors available for a wide variety of favorable, unfavorable and unsatisfied non-bond interactions

Protein

  • Molecular Builders for peptides and nucleic acids
  • Calculation of Solvent Accessibility to identify buried and exposed residues
  • Graphing functionality, including Ramachandran and contact plots
  • Load protein structures directly from the PDB database
  • Generate protein reports to summarize data in protein structures
  • Construct the biologically active unit of a protein from its subunits
  • Clean protein functionality to add missing side-chains, remove disorder and standardize atom naming
  • Enhanced display of protein and nucleic acid sequences and analysis of their composition and alignments
  • Superimpose structures based on tethers, residues and sequence alignment
  • Secondary structure prediction of protein sequences
  • Annotation window to view and edit annotations for nucleic acid and protein sequences
  • Display and contour X-ray electron density maps
  • Basic tools to edit X-ray structures
  • Sampling of side-chain rotamer conformations and interaction analysis

Ligand Design

  • Receptor-ligand interaction surfaces displaying hydrophobicity, hydrogen bonding, aromaticity and more
  • View 2D depiction of molecules in the data table
  • Sketching tools to create new small molecules
  • Modify or build custom 3D small molecules using a tool panel of pre-defined fragments
  • Optimize the geometry of built structures with a fast Dreiding-like forcefield
  • Basic molecular properties can be calculated such as molecular formula and molecular weight
  • Superimpose structures based on molecular overlay using field alignment or tethers
  • Define, display and edit ligand binding sites
  • Generate 2D receptor-ligand interaction plots
  • Analyze the ligand binding patterns between a protein and its bound ligands
  • Manually generate pharmacophore (Catalyst) queries

 

DELIVERING NEW SCIENCE
Molecular simulations are essential to modeling and understand-
ing complex biomolecular systems. The latest release of BIOVIA’s
predictive science application, Discovery Studio, includes anti-
body excipient interactions prediction to enhance biotherapeutics
formulations. Built on BIOVIA Pipeline Pilot™, Discovery Studio®
is uniquely positioned as the most comprehensive, collaborative
modeling and simulation application for Life Sciences discovery
research.
DISCOVERY STUDIO 2022
Part of the 2022 BIOVIA product release series, Discovery Studio
2022 continues to deliver scientific developments in the areas
of biotherapeutics, simulations, and small molecule research.
NEW AND ENHANCED SCIENCE
New! Excipient Interactions Prediction.
• A new protocol, Predict Excipient Interactions, predicts the
preferential interaction of common excipients with antibody
surface residues for antibody formulation1.
• Support Vector Machine and Elastic Net machine learning
models generated from molecular dynamics simulations
predict molecular interactions for 6 formulation excipients
– sorbitol, sucrose, trehalose, proline, arginine·HCl and NaCl.
• Protein surfaces colored by Γ23 values (preferential interaction
coefficients) show interactions of local excipient molecules
compared to local water molecules.
• Used with existing aggregation and viscosity prediction tools, this
enables formulation design earlier in the development process.
Figure 1: Positive values in red indicate higher Γ23 values,
corresponding to more local excipient molecules, while
negative values in blue correspond to more local water
molecule interactions with the antibody.
New! Feature Generation Components.
• Calculate Protein Features and Calculate Sequence Descriptors
components calculate structure- and sequence-based descrip-
tors for machine learning.
• New scripting APIs to support standard and specialized feature
calculations, e.g., a specific interatomic distance for a particular
residue type.
Enhanced! Protein modeling.
• Calculate Protein Formulation Properties protocol now auto-
matically creates aggregation sites and surfaces for analysis
with the View Aggregation Sites tools.
• Positively and negatively charged areas in the Charge Map are
available as Site groups.
• Substructure search for ligand query added to the RCSB Struc-
ture Search protocol, as well all available match types from the
RCSB server.
Enhanced! Simulation enhancements.
• Reduced the memory usage of large solvated systems when
running simulations.
• Assign Forcefield protocol now works with RNA and DNA
templates from custom RTF files.
Enhanced! Various pharmacophore modeling enhancements.
• Nucleic acids supported in the Interaction Pharmacophore
Generation protocol.
• Pharmacophores from a receptor-ligand complex that have
more than 50 non-bond interactions can be built with the
Interaction Pharmacophore Generation protocol.
Figure 2: View the details of aggregation sites.
Figure 3: Nucleic acid interaction pharmacophore.
PARTNER SCIENCE
• CHARMm: Incorporates the academic release CHARMM,
version c44b22.
• NAMD: Distributed with both CPU and GPU editions, version 2.13.
• MODELER: Incorporates the latest release of the academic
MODELLER, version 9.243.
• BLAST+: The BLAST+ version 2.10.1.
• GOLD: Supports GOLD 2021.
COMPATIBILITY
Discovery Studio 2022 is built on BIOVIA Pipeline Pilot 2022.
REFERENCES
1. Cloutier T. K., Sudrik C., Mody N., Sathish H. A., Trout B. L.,
Molecular Pharmaceutics, 2020, 17, 3589-3599.
2. Brooks B. R., Brooks III C. L., Mackerell A. D., Karplus M.,
et
al, J. Comp. Chem., 2009, 30, 1545-1615.
3. Eswar N., Marti-Renom M. A. Webb B., Madhusudhan M. S.,
Eramian D., Shen M., Pieper U., Sali A.,
Current Protocols in
Bioinformatics, John Wiley & Sons, Inc., 2006, Supplement
15, 5.6.1-5.6.30.
• Ligand Profiler protocol includes an option to maximize the
number of features or maximize the pharmacophore fit when
selecting the best fit.
• Screen Library protocol includes an option to report only the
highest fitting pharmacophore for each molecule.
Enhanced! Client functionality enhancements.
• Access the AlphaFold Protein Structure Database from the
Open URL dialog.
• Color proteins from the AlphaFold Protein Structure Database
based on the per-residue confidence score.
• Calculate RMSD and similarity properties without alignment.
• Analyze reports with sortable tables without an active server.
Figure 4: A protein from the AlphaFold Protein Structure
Database colored by the per-residue confidence score.

Related products