Computational Structural and Chemical Biology Core Facility

The Computational Structural and Chemical Biology Core brings customized structural biology and chemical biology insights to your research, facilitating hypothesis generation and guiding experimental design. We offer state-of-the-art molecular visualization, structural analysis, ligand-based modeling, and structure/activity predictions that are designed to accelerate discovery.

Computational Chemical Biology

In partnership with the Vanderbilt Institute for Chemical Biology (VICB), we offer Ligand-Based modeling techniques. For example, if you have validated hits from High-Throughput-Screening (HTS) experiments, we can generate pharmacophores, predict structure-activity relationships (SAR), and perform ligand-based virtual screens on commercially-available compound libraries to increase your hit rate in subsequent HTS experiments.

In cases where ligand-based SAR data are available, they can be combined with structure-based techniques described below, to provide intermolecular structure-function insights.

Computational Structural Biology

The core has expertise in a wide array of structure-based techniques, including but not limited to homology modeling, molecular mechanics, ligand docking, protein-protein docking, and protein design applications. Gaining 3D structural insight into your system often creates opportunities to design more effective experiments and/or create detailed new hypotheses about modes of function.

Contact Us

Please contact us to schedule a consultation via our web form or by using the staff email links below.

The facility is staffed by Scientific Director Jarrod Smith, Ph.D. and Jonathan Sheehan, Ph.D., each bringing a unique set of experience and skills with these methods. CSB faculty Jens Meiler and Terry Lybrand provide expert advice for ongoing project development.

Select Examples

Consult the table below for a partial list of services offered, and select examples of publications from previous projects that were supported by this core.

Service	Description	Example Publications
Ligand-Protein Docking	Production of low energy ligand protein complexes given the high resolution structure or refined homology models for a target protein	Hadac, EM et al, J Med Chem (2006) Kaufmann KW, et al, Proteins (2009) Hight MR, et al, C.C. Research (2014)
Virtual Screening	Pharmacophore hypothesis development and screening of commercially available compound library (e.g. ZINC)	Mueller R, et al, ACS Chem Neurosci (2010) Mueller R, et al, Chem Med Chem (2012)
Protein-Protein Docking	Generation of clustered models for protein / protein interactions given xray crystal or high resolution NMR structures of target protein(s)	Hanson SM, et al, Structure (2008) Kim S, et al, J Biol Chem (2011) Smith JA, et al, Biochem (2014)
Protein Homology Modeling	Generate atomic level protein model(s) given an available xray crystal structure near 30% or greater sequence identity with the target protein	Kaufmann KW et al, Proteins (2009) Stepanovic SV et al, J Physiol (2009)
Pharmacophore Hypothesis	Flexible structure superposition for a series of up to 5 ligands with related biological activity at a target protein (generates starting point for ligand-based virtual screening)	Xiang Z et al, ACS Chem Neurosci (2011) Bhave G et al, Mol Pharmacol (2011)
Molecular Dynamics Simulation	Generation of nanosecond to microsecond timescale ensemble of energy-refined models for target protein from initial homology model or xray crystal structure	Henry LK et al, J Biol Chem (2011) Egli M et al, Biochemistry (2013)
BARD Analysis/Training	Analysis and reporting of promiscuity and structure activity relation from mining the local BARD database to generate novel chemical biology hypotheses / Instruction on upload of data to BARD	deSouza et al, J Biomol Screen (2014)
One-on-One Training	Individual instruction on basic use of computational biology software applied directly to the research project of choice	Fill out the CSB Access form