Structural coverage of the proteome for pharmaceutical applications.

Area of Science:

• Computational drug discovery
• Structural biology
• Genomics

Background:

• Traditional drug discovery relies on single-target structures.
• Proteome-scale analysis for polypharmacology and target deconvolution is limited by structural data.
• A significant 'structure gap' historically hindered in silico approaches.

Purpose of the Study:

• To assess the current structural coverage of the human proteome.
• To determine the feasibility of proteome-wide molecular docking for drug discovery.
• To evaluate the potential for structure-based approaches in target deconvolution and polypharmacology analysis.

Main Methods:

• Survey of publicly available protein structure data.
• Analysis of structural coverage across the human genome.
• Categorization of proteins based on pharmaceutical relevance.

Main Results:

• Human genome structural coverage is now proteome-wide.
• Significant progress in closing the 'structure gap' for most protein categories.
• Structure-based computational methods are becoming viable for large-scale applications.

Conclusions:

• The "structure gap" has been largely closed, enabling proteome-wide structure-based drug discovery.
• Structure-based approaches are now feasible for target deconvolution and polypharmacology.
• The current era supports the widespread application of in silico structure-based methods.