Software Tools for Drug Discovery, Computational Chemistry and Artificial Intelligence

The following are links to software resources to help those researching new drugs and therapies.

Chemical, Molecular and Biological Databases:

Many online database libraries of molecules and proteins have been created as shared resources to be employed and integrated with software tools used for simulation and development.

• PubChem - chemical information
  One can also download current chelator compound digital models (DMSA, DMPS, NBMI, ALA, MiaDMSA, Glutathione, etc)
• BindingDB - molecules with drug-like properties and their binding affinities
• UniProt - protein sequence and function. Used for AI "learning".
• NIH: Chemical structures database (chemical and molecular models including nucleotides, carbohydrates, lipids, peptides, chemically-modified macromolecules, etc)
• ChEMBL - database of bioactive molecules with drug-like properties. ChEMBL primarily stores compound-target interactions (how a small molecule binds to a protein or biological target) rather than direct patient drug-drug interactions.
• NCATS - An open-science platform that shares real-time drug screening data, protocols, and chemical datasets for emerging public health needs and other diseases.
  The National Center for Advancing Translational Sciences (NCATS) provides several key public databases and data portals to support preclinical research, drug discovery, and clinical studies.
• CartBlanche - an interface to ZINC-22, a free database of commercially-available compounds for virtual screening and ligand discovery.
  • ZINC-22 - database
• RCSB: Protein Data Bank (PDB) - hosted by Rutgers, UC San Diego, UC San Diego Supercomputer Center, UC San Francisco
  • PDB: Alpha-Synuclein protein computer data models
• Human Protein Atlas

Also see SMILES - specification in the form of a line notation for describing the structure of chemical species using ASCII strings

• VAE: A SMILES Variational Autoencoder - a deep learning model that translates discrete molecular structures written in SMILES format into a continuous numerical string for automated drug and material design.

Software Models and Resources:

Gone are the days of counting cells in an image. We have software to do that mundane work. Tinker toy chemical models have been replaced by 3D computer models. Even analytics are automated with purpose built data analysis tools.

• Google AlphaFold - pairing DeepMind AI and protein folding
  • AlphaFold Protein Structure Database (EMBL-EBI)
• Fold.it - visual protein folding software for protein research and design
• National Institute of Health (NIH) software: (free open source)
  • ImageJ - Image processing and analysis in Java - microglia item count and astrocytes densities
• Zeiss: software:
  • Axiovision - image analysis
  • ZEN lite - image acquisition from microscope cameras, image processing and analysis
• GraphPad:
  Prism - analysis and graphing solution purpose-built for scientific research
• Certara:
  Phoenix WinNonlin - data processing, graphing and charting, report generation. Pharmacokinetic/pharmacodynamic (PK/PD), and toxicokinetic (TK) modeling.
• CADD: Computer Aided Drug Design
  • Schrodinger - computational chemistry, molecular design, drug formulation and visualization
    Often teams with pharma drug development programs.
  • Wavefun: Spartan - computational chemistry and visualization
  • Biovia (Dassault Systemes):
    Biovia Discovery Studio - biological and physicochemical 3D modeling and simulation.
  • Rosetta - Open source but licensed.
  • Cressset
  • Pharmacelera
  • OpenEye Scientific
  • Chemical Computer Group
  • Acellera
  • Optibrium - drug discovery, design, optimization
• SDF: Structure Data Format - text based chemical structure data file
  Software which can read SDF files:
  • Avogadro - free open source for MS/Win, Mac and Linux. Define, model and visualize 3D molecules. Interfaces with many computational chemistry tools
  • DataWarrior - free open source
  • OpenEye Scientific VIDA
  • iMol - free open source
  • Jmol - free open source Java based viewer for 3D chemical structures, vibration frequency mode animations, etc
  • IQmol - free open source. MS/Win, Mac, Linux. Generate models of molecules.
  • Molekel - free open source
  • ChemSpotlight - free open source
  • Open Babel - free open source
  • SDFReader - free open source
  Tools: Progenesis SDF Studio - A free tool to view, merge and repair SDF and MOL files.
• Computational Chemistry Tools:
  • Gaussian - molecular mechanics, quantum chemistry, coupled cluster calculations
  • ORCA - quantum chemistry, coupled cluster calculations
  • LAMMPS - for solid-state materials (metals, semiconductors) and soft matter (biomolecules, polymers) and coarse-grained or mesoscopic systems.
  • GROMACS - open-source software suite for high-performance molecular dynamics and output analysis.
  • Suite of open source computational chemistry software: OpenChemistry.org - Avogadro, MoleQueue + MongoChem and Tomviz
  • AutoDock Vina - open-source program for simulating molecular docking and how molecules and drug candidates bind to a protein and estimates their binding affinity. It was originally developed at The Scripps Research Institute. Also requires AutoDock Tools for viewer and support tools.
  • Swiss-Model - 3D protein modeling
    works with other tools:
    • Blast - compares protein sequences to sequence databases
    • HHBlits - iterative protein sequence searching
    • MolProbity - validation for 3D structures of proteins
    • HPEPDOCK - predict complex structure between a protein and a peptide
      [server]
    • HDOCK server - Protein-protein and protein-DNA/RNA docking
  • MOPAC: Molecular Orbital PACkage - semiempirical quantum chemistry - free open source for MS/Win, Mac and Linux
  • GAMESS: General Atomic and Molecular Electronic Structure System - quantum chemical calculations. Many code forks exist with huge differences. Free open source for MS/Win, Mac and Linux
  ORCA and Gaussian tend to be more accurate. MOPAC and GAMESS tend to be less computationally demanding.
• De Novo Software; FCX Express - raw flow cytometry data (number of cells or particles in a liquide flow) to report charts

Protein Database: Cryo-EM structure of alpha-synuclein H50Q Narrow Fibril

Molecule Builders, Editors and Viewers:

• VMD: Visual Molecular Dynamics - molecular visualization and animation. Free open source for MS/Win, Mac and Linux. Like Avogadro but more sophisticated.
  Ubuntu install: sudo apt-get install vmd
• PyMol - molecular visualization and animation. Free open source for MS/Win, Mac and Linux. Maintained by Schrödinger.
• Avogadro - free open source for MS/Win, Mac and Linux. Define, model and visualize 3D molecules. Interfaces with many computational chemistry tools.
  Ubuntu install: sudo apt-get install avogadro

Terms and Acronyms:

Term or Acronym	Description
De Novo Design	The process of creating completely new molecules, proteins, or drugs from scratch using physical rules and computers, rather than copying existing natural templates.