Paper Citing NAMD - Abstract
Lindert, Steffen; Maslennikov, Innokentiy; Chiu, Ellis J. C.; Pierce, Levi C.; McCammon, J. Andrew; Choe, Senyon
Drug screening strategy for human membrane proteins: From NMR protein backbone structure to in silica- and NMR-screened hits
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 445:724-733, MAR 21 2014
About 8000 genes encode membrane proteins in the human genome. The information about their drug-gability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, (N) under bar MR spectroscopy, and molecular (DY) under bar namics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins: hypoxia-induced genes HIGD1A and HIGD1B. (c) 2014 Elsevier Inc. All rights reserved.
