Most pharmaceuticals are small organic molecules that work via noncovalent interactions with biological macromolecules. Although drugs have saved or improved countless lives, drug discovery remains an inexact science that involves much trial and error. My research group has been developing fast and theoretically rigorous computer modeling methods to characterize noncovalent protein-ligand interactions. Most of our tools are based on implicit ligand theory, a theoretical framework that I derived to predict how tightly molecules bind and how they influence the population of conformations accessed by their targets. At this point, we have established that our methods are able to reproduce results of more computationally expensive approaches. We are working on making them more efficient and feasible to use with large libraries of chemical compounds. We have also advanced the theory of end-point binding free energy methods, in which binding affinity is predicted based on molecular simulations of the bound complex without a time-consuming series of intermediate thermodynamic states.
Additive manufacturing (AM) allows the creation of components in a layer-by-layer, additive fashion, which offers enormous geometrical freedom compared to conventional manufacturing technologies. It is widely recognized that topology optimization is essential to exploit the design space AM allows. However, overhang limitation in additive manufacturing prevents the direct production of topology optimized parts since extra support is usually required during printing and needs to be removed during post-processing. Lately, a layerwise filter has been incorporated in density-based topology optimization on uniform structured meshes for print-ready designs. The limitation of this technique is that the minimum allowable overhang angle (the angle a down-facing surface has with the base plate) is restricted to 45 degree. In practice, smaller overhang angles cause more roughness. At times, a greater overhang angle is desired due to smoothness requirement. In this work, we present a multi-layer based overhang constraint that allows minimum overhang angle greater than 45 degree without changing the element aspect ratio of the mesh. The newly developed constraint is demonstrated on 2D examples while it can be extended to 3D.
Hongyu (Alice) Zhu is a senior research engineer in System Dynamics and Optimization Group at United Technologies Research Center. She is currently working on optimal design for a wide range of systems including additive manufacturing, fire suppression system, aircraft cargo power driven unit configuration, etc. She graduated from University of Texas at Austin in 2017 with a PhD in Computational Science, Engineering and Mathematics, and joined United Technologies Research Center afterward.