Protein Dynamics for Drug Design

The image shows the aminoacyl-transfer-RNA (yellow) caught in the act of delivering its amino acid (green) to the growing protein hanging off the peptidyl-transfer-RNA (cyan). The ribosome (large subunit in white and small subunit in purple) uses the transfer RNA molecules to read the genetic information from the messenger RNA (green). For visualization purposes, the top portion of the ribosome is cut away so that the transfer RNA molecules are visible. Credit: Los Alamos National Laboratory

Kevin Y. Sanbonmatsu, of Los Alamos National Laboratory's Theoretical Biology and Biophysics Group, accomplished simulations of the decoding center of the ribosome. Simulating 2.64 million moving atoms, these representations are larger-by a factor of 6-than the largest published million-atom computer simulation in biology to date. These first-ever simulations generated the key finding that transfer ribonucleic acid must be flexible in two locations before protein synthesis can occur and also identified new ribosomal areas in which mutations and protein synthesis-blocking antibiotics could be misread or not accurately understood. His research has important implications in the rational design of antibiotics such as gentamicin and doxycycline. This work has made it possible for other researchers to conduct million-atom simulations of the entire ribosomal function. Sanbonmatsu's work also led him to establish a landmark computational biology research program at LANL and to obtain a 5-year grant from the National Institutes of Health.

Kevin Y. Sanbonmatsu, Simpson Joseph, and Chang-Shung Tung, "Simulating movement of tRNA into the ribosome during decoding (pdf)," PNAS 102, 44 (November 1, 2005)