Molecular Informatics Core

Integrating biomolecular structure information into therapeutic development

Understanding the molecular basis of action and biological effects of therapeutic agents is greatly enhanced by a detailed understanding of molecular sequence and structure. The examination of structure-function relationship and evolution of protein components complements the coverage provided by high-throughput efforts for the discovery of chemical compounds with desired activity, as well as, target discovery and characterization by siRNAs. It can also guide the rational design of improved compounds and experimental screening efforts.

The Molecular Informatics Core (MIC) facilitates sophisticated use of molecular structure information by providing access to databases, state-of-the-art software, and expert support for protein sequence and structure analysis, protein structure modeling, characterization of protein-ligand interactions, and virtual screening. The MIC will provide support for the integration of these advanced structural bioinformatics tools into research projects, grant proposals, and publications.

Working closely with other core facilities at the ETI, in particular the Integrated Screening Core, the MIC will support target characterization, lead discovery, and lead optimization.

The MIC offers research expertise and support in the following areas:

1. Target Characterization

• Protein structure modeling for target proteins
• Structure and sequence-based similarity analysis of proteins
• Phylogenetic and structural analysis of target protein families
• Identification of potential ligand binding sites in protein structures
• Advanced molecular graphics for grant proposals, publications, and presentations

2. Small-molecule Virtual Screening and Docking

• High-throughput computational screening of small-molecule libraries, containing more than 100,000 compounds, against experimental and predicted target protein structures
• Construction of targeted libraries for HT chemical screening based on virtual screening results
• Targeted docking of selected compounds into experimental and predicted target protein structures

3. Protein-Ligand Interaction Characterization and Optimization

• Structural modeling of protein-ligand complexes and energetic characterization of interactions
• Identification of affinity and selectivity determining residues in the target protein
• Support for structure-based refinement of protein-ligand interactions to enhance affinity and selectivity
• Rational Design of target protein mutants for experimental validation
• Protein-Protein Docking to support the validation of macromolecular interactions

User Support

The MIC staff assists researchers with the development and execution of computational strategies to address specific research questions. Through an initial consultation MIC staff can quickly establish the computational feasibility of the project and identify the structural bioinformatics approach that is required to address it.

For more information regarding MIC functions and services, or to schedule an initial consultation, please contact Roberto Sanchez, PhD at roberto.sanchez@mssm.edu.