Nipah

Nipah models nine Nipah viral proteins and identifies peptide inhibitors targeting G, F, and M and small-molecule inhibitors targeting F, G, M, N, and P using homology and ab initio modeling, docking, molecular dynamics, and resistance analysis to support therapeutic development.

Key Features:

• Comprehensive Protein Targeting: Considers each of the nine Nipah viral proteins as potential therapeutic targets.
• Peptide and Small Molecule Inhibitors: Identifies putative peptide inhibitors targeting G, F, and M proteins and small-molecule inhibitors for F, G, M, N, and P proteins via computational approaches.
• Structural Characterization: Increases available structural data for Nipah viral proteins by approximately 90% compared to Protein Data Bank (PDB) entries.
• Molecular Dynamics Simulations: Employs molecular dynamics simulations on designed protein–peptide complexes to assess stability and estimate binding strengths.
• Resistance Analysis: Analyzes sequences from multiple viral strains for sensitivity to inhibitor binding and conservation patterns of amino acids across outbreaks.
• Lead Compound Identification: Designed four peptide inhibitors and predicted 70 small molecules, 13 of which are high confidence, against three and five Nipah proteins respectively.

Scientific Applications:

• Drug Development: Provides lead compounds and detailed structural models for experimental validation and hypothesis testing in drug development.
• Vaccine Research: Aids vaccine design by highlighting conserved protein structures and amino-acid conservation patterns across strains.
• Epidemiological Studies: Informs analyses of sequence variation and potential resistance mechanisms across Nipah virus outbreaks.

Methodology:

Homology and ab initio modeling to construct 3D protein models; computational peptide design and small-molecule docking to predict interactions; and molecular dynamics simulations to evaluate complex stability and estimate binding affinities.