Increasing the strength of binding between a molecule and a receptor is an important technique in the design of effective drugs. Binding affinity synthesizes molecules that are already in the shape that they will take when bound to a receptor. This technique works because it decreases the binding entropy, which increases the overall binding affinity. The research addresses biological and medical challenges from single molecules to the genome with high-performance computing and theory. In collaboration with other experimental groups, the researchers use computer modeling and simulations to understand these complex biomolecular systems and to discover molecules for treating disease and improving human health. Image Caption 1: Frame from the molecular dynamics (MD) simulation of constrained and unconstrained molecule bound to receptor. These calculations revealed that the origin of the constrained molecule (purple) and unconstrained molecule (pink) have similar conformations when bound to the receptor. Image Caption 2: Frame from the molecular dynamics (MD) simulation of the constrained and unconstrained molecule free in solution. In solution, the unconstrained molecule (pink) is capable of forming more compact structures that allow hydrogen bonds (green dotted line) to be formed with the phosphate group (represented by the yellow and red atoms).
Yue Shi of the The Ren lab at The University of Texas at Austin probed the origin of this entropy paradox with molecular dynamics simulations run on the Lonestar and Ranger supercomputers at TACC. TACC staff used VMD to load the molecular dynamics data and to set up the model and the Tachyon Parallel Ray Tracer to render it. Their group used approximately 2 million CPU hours on Ranger and about 1 million CPU hours on Lonestar.