Structural Biology at NIH - Computational structural biology

* Senior Investigator: David Covell

* Affiliation: Biomolecular Structure Group, PRI/Dyncorp/NCI.

* Research: Macromolecular structure analysis. Computational methodologies are being developed to better understand rudimentary relations between molecular structure and biological function. Applications include the use of simplified lattice models to predict 3D structure, models of intermediate detail to assess candidate locations for ligand binding, and detailed atomic models to investigate the hydration enthalpy-entropy relationships to structural stability and ligand binding. Efforts are aimed at providing information useful for structure determination as well as ligand inhibitor design.

* Personnel/Resources: Staff at the Biomedical Supercomputing Resource, Frederick, Maryland. Hardware includes a mainframe supercomputer, SGI, SUN and Digital workstations, and a complete visualization laboratory.

* Publication:

D.G. Covell (1992). Proteins: Structure Function and Genetics 14:409-420. Folding protein alpha-carbon chains into compact forms by Monte Carlo methods.

D.G. Covell, & R.L. Jernigan (1991). Proteins: Structure, Dynamics and Design, ESCOM Science Publishers B..V. Leiden, 346-351. Compact protein conformations.

D.G. Covell, & R.L. Jernigan (1990). Biochemistry 3287-3294. Conformations of folded protein restricted spaces.

S.C.J. Sumner, K.S. Gallagher, D.G. Davis, D.G. Covell, R.L. Jernigan, & J.A. Feretti (1990). J. Biomol. Str. Dyn. 8:687-707. Conformational analysis of the tachykinins in solution: substance P, and physalaaemin.

R.L. Jernigan, H. Margalit, & D.G. Covell (1989). "Theoretical Biochemistry and Molecular Biophysics", Adenine Press: p.69-76. Coarse graining conformations: a peptide binding example.

* Contact: Dr. D. Covell, Bldg. 430. PRI/Dyncorp, NCI, Frederick, MD 21702.

Tel: (301) 846-5785 Fax: (301) 846-5762

Figure: Candidate positions for inhibitor ligands (red, purple & yellow) against HIV-1 protease (grey).