Phase

Phase is an intuitive pharmacophore modeling solution developed by Schrödinger for ligand- and structure-based drug design. It enables researchers to assess compounds based on the steric and electronic features of molecules known to have biological activity, making it a powerful tool for both lead optimization and virtual screening campaigns.

Phase employs a unique common pharmacophore perception algorithm that helps create an understanding of an unknown binding site even in the absence of a protein structure. It is designed for medicinal chemists and computational scientists seeking to identify novel hits and chemotypes likely to bind to a target receptor.

Key Capabilities

• Easily set up, execute, and analyze pharmacophore screening through an intuitive user interface.
• Screen and determine the spatial arrangement of chemical features that interact with a receptor, using binding information to identify novel compounds and chemotypes likely to bind to the target.
• Create pharmacophore hypotheses from protein-ligand complexes, apo proteins, or from ligands alone, with the ability to selectively merge hypothesis features to create hybrid models.
• Exercise precise control over pharmacophore creation, generation, and screening workflows.
• Rapidly and thoroughly sample conformational, ionization, and tautomeric states, with optional minimization using the best-in-class OPLS4 force field to create a Phase database.
• Access fully prepared databases of purchasable compounds from Enamine, MilliporeSigma, MolPort, and Mcule for out-of-the-box screening.

Commercial Library Access

• Schrödinger has partnered with leading compound providers to deliver access to commercial databases of fragments, lead-like, near drug-like, and drug-like compounds.
• Available libraries range from millions to billions of compounds, encompassing a vast chemical space for comprehensive virtual screening.
• Pre-prepared databases enable researchers to begin screening immediately without additional library preparation steps.

Available Tutorials and Learning Resources

• Ligand-Based Screening for Ultra-Large Libraries with Quick Shape and the Hit Analyzer: Perform Quick Shape screening on a library of 20,000 compounds and analyze the results.
• Ligand-Based Virtual Screening Using Phase: Create and analyze pharmacophore hypotheses from congeneric and diverse ligand sets.
• Structure-Based Virtual Screening Using Phase: Create and analyze pharmacophore models generated from a protein-ligand complex.
• Rapid Screening of Chemical Libraries with GPU Shape: Perform rapid shape-based screening of a 20,000 compound chemical library using GPU Shape.
• Online certification courses and self-paced molecular modeling training are available, including access to Schrödinger software and support.

Related Computational Technologies

• Shape Screening: Efficient ligand-based virtual screening of millions to billions of molecules.
• Glide: Industry-leading ligand-receptor docking solution.
• Epik: Rapid pKa and protonation state prediction tool.
• ConfGen: Accurate and efficient conformational search solution.

Phase integrates seamlessly within the broader Schrödinger life science platform, complementing tools for docking, conformational sampling, and protonation state prediction. Its application has been demonstrated across a wide range of published research, including inhibitor discovery, QSAR studies, and multi-target pharmacophore modeling, underscoring its versatility across diverse drug discovery programs.