Don Shillady

Dept. of Chemistry   Virginia Commonwealth University   1001 W. Main St.   Richmond, VA 23284-2006	Tel: 804-828-1298 Fax: 804-828-8559 E-mail: ddshillady@vcu.edu
Web: http://www.people.vcu.edu/~dshillad/
Research: Application of molecular orbital methods to large molecules

BBSI project: Molecular structure of the HIV-1 protease

Unlike their human hosts, HIV manufactures its proteins in long concatenated strings, called polyproteins. The virus therefore needs a mechanism to divide the chain into separate functional proteins. This is accomplished by a specific protease. Since the protease is essential for HIV viability, it stands out as a possible target for pharmaceutical intervention. Understanding the structure of the enzyme may shed light on its function and may point to possible inhibitory molecules.

The structure of the HIV-1 protease has been determined to 2.1 micron resolution. We have been using a program to take the structure to a finer level, via molecular orbital calculations. The present program is limited, however, by its inability to handle molecules larger than 4000 atoms and to adequately account for hydrogen bonds, very important in protein structure. We shall extend the program to overcome these limitations.

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