PsychoProt

PsychoProt analyzes substitution tolerance across protein sequences to quantify how amino acid physicochemical and structural properties shape sequence variability and functional constraints.

Key Features:

• Structure-Based Analysis: Identifies spatial patterns of substitutions relative to functional regions, reporting low substitution frequency within 7 Å of the active site and increasing permissiveness up to 15–20 Å.
• Quantitative Modeling of Substitution Patterns: Models over one-third of residue substitution patterns using monotonic dependencies on amino acid descriptors such as volume, steric hindrance, hydrophobicity, solubility, charge, and hydrogen bonding capacity.
• Protein Core Constraints: Reveals that amino acid volume and steric properties constrain the protein core while hydrophobicity and solubility drive hydrophobic clusters beneath the surface and salt-bridge or polar networks at the surface.
• Trait-Sequence Relationships: Quantifies links between sequence variation and protein traits to uncover subtle and unexpected relationships between chemistry and evolution.
• Functional Implications: Examines how specific traits are compromised during gain-of-function mutations, informing evolutionary interpretation and rational protein engineering.
• High-resolution Mutational Maps: Utilizes high-resolution maps derived from deep sequencing of mutant libraries, including studies of TEM lactamase, to assess substitution tolerance across all positions within functional enzymes.

Scientific Applications:

• Molecular Evolution Studies: Integrates structural biology and biophysics to analyze constraints on protein sequences imposed by functional and structural contexts.
• Protein Design and Engineering: Provides a framework to predict how changes in amino acid properties affect protein stability and function for the design of novel proteins with desired traits.
• Deep Mutational Scanning Analysis: Interprets deep sequencing data from mutant libraries (e.g., TEM lactamase) to identify substitution tolerance patterns and governing amino acid descriptors.

Methodology:

Analyzes high-resolution maps derived from deep sequencing of mutant libraries (such as TEM lactamase) to assess substitution tolerance across positions and identify amino acid descriptors that govern sequence variability.