E-Volve

E-Volve models and analyzes mutations in protein complexes to assess structural and functional impacts on the SARS-CoV-2 spike protein and its interactions with antibodies and the ACE2 receptor.

Key Features:

• Mutation Modeling: Uses Modeller to generate structural models of protein complexes incorporating specified mutations.
• Variant Analysis: Analyzes variants of concern B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), producing contact maps and heat maps to visualize interactions in spike-antibody and spike-ACE2 complexes.
• Interaction Mapping: Highlights interface changes due to mutations, with focus on alterations such as N501Y and E484K that affect antibody neutralization and receptor affinity.
• Electrostatic and Hydrophobic Analysis: Assesses electrostatic surface complementarity and identifies new hydrophobic bonds to evaluate effects on binding affinities with antibodies P17 and BD-368-2 and the ACE2 receptor.
• Molecular Dynamics Simulations: Performs molecular dynamics simulations followed by Poisson-Boltzmann calculations to evaluate changes in complementarity and protein conformational equilibrium.
• Conformational Disorder Analysis: Examines local structural disorder, including the loop α1'/β1', to assess potential effects on antibody affinity.

Scientific Applications:

• Research on Viral Evolution: Characterizing how specific mutations alter viral behavior and contribute to lineage evolution, including immune escape mechanisms.
• Antibody Efficacy Studies: Evaluating the impact of mutations on antibody neutralization to inform vaccine and therapeutic assessments.
• Receptor Binding Analysis: Investigating changes in ACE2 binding affinity that may influence transmissibility and pathogenicity.

Methodology:

Structural modeling with Modeller; generation of contact maps and heat maps; interaction/interface mapping highlighting mutations (e.g., N501Y, E484K); electrostatic surface complementarity and hydrophobic bond analysis; molecular dynamics simulations followed by Poisson-Boltzmann calculations; and analysis of local conformational disorder (loop α1'/β1').