Andrej Sali Lab

Andrej Sali Lab provides computational tools for comparative protein structure modeling and analysis to predict three-dimensional protein structures and assess functional impacts of sequence variation.

Key Features:

• MODELLER: Implements comparative modeling by satisfaction of spatial restraints to construct three-dimensional protein models from homologous templates.
• MODWEB: Automates comparative modeling by integrating PSI-BLAST, IMPALA, and MODELLER for template search, alignment, and model generation.
• MODLOOP: Performs automated loop modeling using MODELLER to model regions lacking template information.
• MOULDER: Implements a resource-intensive protocol for constructing comparative models from distant homologous structures.
• MODBASE: Contains an annotated database of comparative models for sequences related to known structures.
• MODVIEW: Visualizes multiple sequences and structures for comparative analysis.
• SNPWEB: Predicts functional impacts of single amino acid substitutions based on protein structure.

Scientific Applications:

• Drug discovery: Use comparative models to predict ligand binding sites and protein–small molecule interactions.
• Disease mechanism analysis: Investigate molecular mechanisms of diseases linked to mutations that alter protein structure and function.
• Genetic variation analysis: Assess functional consequences of single amino acid substitutions to inform personalized medicine and evolutionary biology.

Methodology:

Comparative modeling using known protein structures as templates; satisfaction of spatial restraints derived from sequence alignments and structural data; template search and alignment using PSI-BLAST and IMPALA; model building with MODELLER including automated loop modeling (MODLOOP) and a protocol for distant homologs (MOULDER).