Structural Biology Drug Discovery Shared Resource

Overview of Services

The SBDDSR serves as a portal for access to consultation, state-of-the-art crystallization and X-ray diffraction equipment, recombinant protein production, high-performance computing and in silico drug screening, and medicinal chemistry and technical support. The team will meet the investigator at all levels of structure determination, computational needs and compound indentification and optimization.

 The Structural Biology team has expertise in the production of recombiant proteins, assay development, macromolecular crystallography, and experimental structure determination.

• Consulting on all aspects of protein expression, purification, and feasibility of structure determination.
• Identification of crystallization conditions and possible other existing structures.
• Access to X-ray diffraction facility.
•  Determination of the molecular structure through collaboration.

 Our Computational expertise focuses on the structural and dynamical studies using molecular dynamics and statistical analysis,  virtual screening of compound libraries,  computational refinement of lead compounds, and other biophysical modeling. Initial simulations, screens, or database queries are conducted to determine if the models are providing reasonable preliminary results. 

• Consultation to determine if the problem is amenable to computation. 
• Decide what sort of computations need to be performed.
• Calculations that we can readily perform include molecular dynamics, protein-protein docking, protein-ligand docking, virtual screening and refinement, and related statistical analysis. AI-based methods, quantum mechanical calculations and other mathematical modeling may be possible.

 Our Medicinal Chemistry expertise focuses on the identification and validation of hit compounds from in silico and experimental HTS screens. Once hits have been identified, fresh powder of the hit compounds and structurally-related compounds are purchased from commercial vendors for validation. Once validated, the compound scaffold is evaluated for synthetic route design and in-house synthesis of a select number of analogs as proof of concept. At this point, extramural funding applications will be sought to expand the synthesis of compounds and the structure-activity-relationship portfolio. 

• Consultation to determine if inhibitors of a potential target are already available
• Evaluation of in silico and experimentally-obtained hits for synthetic route and patent literature
• Design, synthesis and purification of small molecule compounds for testing via in vitro assays with recombinant proteins and cell-based models.

Leaders

Todd Lowther, PhD
Co-Director
Professor, Biochemistry

Todd.Lowther@wfusm.edu

Tom Hollis, PhD
Co-Director
Professor, Biochemisty

Thomas.Hollis@wfusm.edu

Freddie R. Salsbury Jr., PhD
Co-Director
Professor, Physics (WFU)

salsbufr@wfu.edu

Terry Smalley, PhD
Assistant Director
Assistant Professor, Biochemistry

Terrence.Smalleyjr@wfusm.edu

Location and hours of operation

Links and Resources

1. Structual Biology and Drug Discovery Shared Resource
2. Center for Structural Biology

Citation Resources

Cite the P30 CCSG

The authors wish to acknowledge the support of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center Structural Biology and Drug Discovery Shared Resource, supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

NIHMS Guidelines for Authors

Authors should also make sure that all publications are processed by the National Institutes of Health Manuscript Submission (NIHMS) to obtain a PubMed Central reference number (PMCID), per NIH guidelines.

External Funding Application “Facility” Description

Review the facility description of this Shared Resource on pages 2-5 of the  AHWFCCC boilerplate. 

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Contacts