Abstract 2151 First Year Chemistry CURE: An Introduction to Chemical Thinking through the Lens of Antimalarial Drug Design

This CURE was designed for introductory chemistry students in a lab class of 18-24 students at three different institutions, University of San Diego, Southwestern Community College and Gaston College. and can be taught as a full semester or a 4-6 week modular CURE within a standard laboratory class. It is suitable for students in an introductory level chemistry class and requires no specialized knowledge. This CURE is readily adaptable to any disease or potential drug target as well as other aspects of drug discovery and optimization. Overall, the course has a set of department required STUDENT GOALS: 1) Students will appreciate what a good research project entails and will develop approaches to develop a novel hypothesis and present a proposal for their project. 2) Students will learn how to design and execute experiments to test their hypothesis, will learn appropriate data analysis approaches, and will appreciate the importance of accurate documentation of their work and reproducibility of their experiments. 3) Students will develop a description of their research project in written, poster, or a slide presentation suitable for verbal presentation. As well as a series of RESEARCH GOALS: 1) To develop ideas for potential lead compounds that can distinguish between pathogen and host homologs of a potential drug target; 2) To initiate approaches for optimizing the potential of lead compounds to increase their suitability as candidates for future drug design. The research theme is a perennial problem facing drug development, how can you achieve specificity for a pathogen target when host homologs exist. The CURE starts with discussions of the target enzyme, Malate Dehydrogenase (MDH), what it does in both pathogen and host, and introduces some basic ideas of both orthosteric and allosteric drugs. Students then decide which approach they want to pursue, do background reading into Malaria, and start to pose questions of what they need to know or be able to do to uniquely target the pathogen MDH. Using bioinformatics and protein visualization to develop ideas for compounds they would like to screen (including high-throughput screening, screening extracts of natural products e.g., herbal extracts, etc.), making a hypothesis, and developing their research proposal. They screen potential "drug-like" molecules based on known or potential orthosteric ligands using enzyme inhibition kinetics, and explore potential cryptic allosteric sites computationally all the time using pathogen target and human homologs. They explore Lipinsky rule of 5 properties both experimentally, determining logP, or structure-activity relationship properties computationally. They learn to apply appropriate data analysis and display approaches, and accurately record experimental details and data archiving. They select, based on their hypothesis and actual data they collected, which experiments need repeating to validate their evidence based conclusion. Each stage of the course uses peer review of presentations on critical elements of the research enterprise and students have the chance to revise based on feedback prior to grading. Depending on the approach they chose, there are various potential stake holders. Students are encouraged to think about the relevance of their project and communicate as appropriate their plans early in the course and research products at the end of the course, explaining why there is a continual need for new antimalarial drugs and what approach they have chosen to pursue. This work was supported by NSF-1726932 EHR-IUSE: An Interdisciplinary Faculty Community Using a Protein-focused CURE to improve student learning. Ellis Bell PI.