Structure-Based Drug Discovery Services (SBDD) works on both a collaborative as well as a fee-for-service basis and also provides subscriptions for frequent users. We work with internal and external researchers. Some of our services for researchers at the Icahn School of Medicine at Mount Sinai are subsidized by the institution. Our fee-for-services is determined after an initial consultation to determine the needs of a project. Below are descriptions of the most frequent SBDD services.
Virtual screening (aka in silico screening) refers to the computational screening of small-molecule libraries using the three-dimensional structure of a target protein (target-based virtual screening) or the chemical structure of known active compounds (ligand-based virtual screening). Software is used to match each small-molecule compound in the library to a binding site in the target protein or to the structure of a known active compound. The output of virtual screening is a ranked list of compounds predicted to bind to the target protein (or mimic the active compound in the case of ligand-based virtual screening). We provide virtual screening services of the Mount Sinai small-molecule libraries (~115,000 compounds), National Cancer Institute library (~265,000 compounds), and of libraries of commercially available compounds (>20 million compounds). Virtual screening can usually be completed in a few weeks.
While three-dimensional (3D) structures for many proteins are available, most proteins have not had their structure determined experimentally. For these proteins it is often possible to obtain a model of its 3D structure via comparative or homology modeling, which takes advantage of the known structures of homologous proteins. These models are frequently of sufficient quality to be used as starting points for virtual screening. We provide protein structure modeling services and offer guidance to make decisions about the suitability of models for virtual screening and other applications.
Identifying the sites to which small-molecules are likely to bind is useful to guide virtual screening, mutagenesis experiments, and more. We provide methods for the identification of ligand binding sites in protein structures.
The SBDD Core provides services to identify small-molecules that are similar to existing hits or new compounds with known bioactivities. This facilitates the identification of tool compounds for target validation and generating initial structure-activity relationship (SAR) data for compound identified in virtual (SBDD) or physical (Integrated Screening Core) small-molecule screens.
We provide molecular graphics services for the preparation of high-quality images and movies of molecular structures for publications, grants, and presentations.
To support grant applications, we provide text describing our capabilities or specific services as needed for a proposal. Additionally, we can provide descriptions of tailor-made computational strategies to support specific aims of a proposal.
Our staff has expertise in a number of Structural Bioinformatics and Molecular Modeling approaches to analyze protein sequences, protein structures, protein-ligand interactions, and small-molecule structure.