Selecton

Selecton identifies site-specific selection in protein sequences by comparing synonymous (K(s)) and non-synonymous (K(a)) substitution rates and estimating the per-site omega (ω) ratio to infer positive and purifying selection.

Key Features:

• Ratio Calculation and Visualization: Computes the per-amino-acid-site K(a)/K(s) (ω) ratio and represents ω values using a color-coding scheme.
• Evolutionary Models: Implements multiple evolutionary models, including a mechanistic-empirical model that accounts for the physicochemical properties of amino acids.
• Statistical Support and Significance Testing: Provides statistical support for ω estimates and tests the statistical significance of site-specific scores for positive or purifying selection.
• Molecular Surface Projection and 3D Mapping: Projects per-site selection estimates onto protein three-dimensional structures and molecular surfaces to reveal spatial clusters of selected residues.
• Genetic Code and Phylogeny Options: Accommodates different genetic codes and accepts user-provided phylogenetic trees for analysis.

Scientific Applications:

• Molecular Evolution: Identify sites under positive or purifying selection to characterize evolutionary pressures acting on proteins.
• Structural Bioinformatics: Map selection patterns onto protein structures to infer the functional and adaptive significance of residues.
• Functional Residue Prediction: Highlight candidate functional or adaptive residues to guide experimental validation.
• Drug Design and Targeting: Inform drug design by identifying evolutionarily conserved or variable regions within protein structures.

Methodology:

Computes K(a) and K(s) per site and derives ω (K(a)/K(s)); applies multiple evolutionary models including a mechanistic-empirical model that incorporates amino acid physicochemical properties; performs statistical significance testing of site-specific ω estimates; maps selection estimates onto protein 3D structures and molecular surfaces; accepts different genetic codes and user-supplied phylogenetic trees.