Computational studies of chronic beryllium disease

INOR 943

S Gnanakaran, gnana@lanl.gov, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, MS K710, Los Alamos, NM 87545, Brian L. Scott, Chemistry Division, Los Alamos National Laboratory, MS J514, Los Alamos, NM 87545, Angel E. Garcia, Department of Physics, Applied Physics and Astronomy, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, and T. Mark McCleskey, tmark@lanl.gov, Chemistry Division, C-SIC, Los Alamos National Lab, MS J514, Los Alamos, NM 87544.
Beryllium causes the Chronic Beryllium Disease (CBD), a human granulomatous lung disease. Molecular aspects of Beryllium chemistry in the context of biological systems are not well understood. In this computational study, we present structural aspects of major histocompatibility complex class II alleles that are most common among CBD patients. The sequences of CBD associated alleles reveal several carboxyl rich regions in the peptide-binding cleft. &beta1 chain of human leukocyte antigen DP (HLA-DPB1) has a K69E that has been implicated as a genetic marker for predisposition to developing CBD. We have carried out all-atom molecular dynamics simulations on two structural models of HLA-DP; an allele associated with CBD (*0201) and one that is not (*0101). Comparison of disease and non-disease alleles reveals that the effect due K69E mutation is non-local and cooperative. Importantly we identify potential binding sites and interactions of carboxyl triads that can be exploited for allele specific genotyping.
 

Bioinorganic Modeling
1:30 PM-5:30 PM, Wednesday, 13 September 2006 Moscone Center -- Room 307, Oral

Division of Inorganic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006