Search for: All records

The discovery of new drugs is a time consuming and expensive process. Methods such as virtual screening, which can filter out ineffective compounds from drug libraries prior to expensive experimental study, have become popular research topics. As the computational drug discovery community has grown, in order to benchmark the various advances in methodology, organizations such as the Drug Design Data Resource have begun hosting blinded grand challenges seeking to identify the best methods for ligand pose-prediction, ligand affinity ranking, and free energy calculations. Such open challenges offer a unique opportunity for researchers to partner with junior students (e.g., high school and undergraduate) to validate basic yet fundamental hypotheses considered to be uninteresting to domain experts. Here, we, a group of high school-aged students and their mentors, present the results of our participation in Grand Challenge 4 where we predicted ligand affinity rankings for the Cathepsin S protease, an important protein target for autoimmune diseases. To investigate the effect of incorporating receptor dynamics on ligand affinity rankings, we employed the Relaxed Complex Scheme, a molecular docking method paired with molecular dynamics-generated receptor conformations. We found that Cathepsin S is a difficult target for molecular docking and we explore some advanced methods such as distance-restrained docking to try to improve the correlation with experiments. This project has exemplified the capabilities of high school students when supported with a rigorous curriculum, and demonstrates the value of community-driven competitions for beginners in computational drug discovery.

 

Large-scale real-time analytics services continuously collect and analyze data from end-user applications and devices distributed around the globe. Such analytics requires data to be transferred over the wide-area network (WAN) to data centers (DCs) capable of processing the data. Since WAN bandwidth is expensive and scarce, it is beneficial to reduce WAN traffic by partially aggregating the data closer to end-users. We propose aggregation networks for per- forming aggregation on a geo-distributed edge-cloud infrastructure consisting of edge servers, transit and destination DCs. We identify a rich set of research questions aimed at reducing the traffic costs in an aggregation network. We present an optimization formula- tion for solving these questions in a principled manner, and use insights from the optimization solutions to propose an efficient, near-optimal practical heuristic. We implement the heuristic in AggNet, built on top of Apache Flink. We evaluate our approach using a geo-distributed deployment on Amazon EC2 as well as a WAN-emulated local testbed. Our evaluation using real-world traces from Twitter and Akamai shows that our approach is able to achieve 47% to 83% reduction in traffic cost over existing baselines without any compromise in timeliness.