Mechanosensitive Piezo1 and Piezo2 channels transduce various forms of mechanical forces into cellular signals that play vital roles in many important biological processes in vertebrate organisms. Besides mechanical forces, Piezo1 is selectively activated by micromolar concentrations of the small molecule Yoda1 through an unknown mechanism. Here, using a combination of all-atom molecular dynamics simulations, calcium imaging and electrophysiology, we identify an allosteric Yoda1 binding pocket located in the putative mechanosensory domain, approximately 40 Å away from the central pore. Our simulations further indicate that the presence of the agonist correlates with increased tension-induced motions of the Yoda1-bound subunit. Our results suggest a model wherein Yoda1 acts as a molecular wedge, facilitating force-induced conformational changes, effectively lowering the channel’s mechanical threshold for activation. The identification of an allosteric agonist binding site in Piezo1 channels will pave the way for the rational design of future Piezo modulators with clinical value.

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IntroductionApplied practice experiences are essential components of the Masters of Public Health (MPH) curriculum. The objective of this study was to examine students’ perspectives on the skills and expertise they developed in an MPH course offering applied practice opportunities.MethodsOf 236 students who took the course from 2008 to 2018, email addresses were obtained for 212 and 104 completed the consent form. Following consent, reflection essays were de-identified and analyzed using a rapid qualitative analysis approach. The essays addressed students’ learning experiences and application of the competencies for MPH programs set by the Council for Education in Public Health (CEPH). Deductive and inductive analytical lenses were used to identify the key lessons learned by each cohort of students. Semi-structured guides and matrixes for essay analysis were created using assignment instructions and CEPH competencies.ResultsAlthough the reflection paper assignment varied across the years, commonalities were observed in the student reflections. Key themes included turning theory into practice, navigating the complex environment of public health practice, skill building, critical self-reflection, challenges encountered, and elements that facilitated project success. Students reported developing practical skills, such as planning for independent research (e.g., preparing for institutional review board (IRB) submission, consulting with faculty and other experts), identifying realistic approaches for data extraction during chart reviews and analyses of electronic medical records, and disseminating findings for diverse stakeholders and audiences. Students also reported strengthening cross-cutting skills such as communication, teamwork, and problem-solving that were useful for navigating power dynamics and balancing competing interests and expectations. Students explored their identity as public health professionals as they navigated the dynamics of public health practice.ConclusionThe applied practice experience served as a valuable tool for knowledge and skills acquisition. Moreover, it served as an opportunity for students to engage with the unique organizational cultures of their respective community partners and to deepen their understanding the complexities of conducting meaningful community-engaged research.ImplicationsThis study demonstrates the utility of analyzing students’ critical self-reflections as a tool for exploring learning experiences when training future public health professionals. The findings can help educators design future applied practice experiences.

sampling (REUS) molecular dynamics simulations [2]. REUS is a powerful conformational sampling method to overcome energy barriers. We applied this method to the HDAC3-T247 system and HDAC2-T247 system. These have very similar amino-acid sequences and similar structures. From results of these simulations, we obtained free energy landscapes. The results of these calculations show that the docked state is the most stable in the HDAC3-T247 system but in the HDAC2-T247 system, the docked state is less stable than undocked states. These results agree with experimental data. In this poster, we present these results. References:[1] T.

various peptide concentrations and pH levels. The absorbance transitions are sensitive to the formation of the electronically conductive J-aggregate, allowing for rapid spectroscopic identification. Fluorescence spectroscopy, circular dichroism, and dynamic light scattering were also used to assess J-aggregate formation. The peptides were shown to induce the formation of J-aggregates up to solution pH 3.0, but maintains the ability to bind porphyrin at neutral pH. Notably, the peptides were shown to adopt an unstructured conformation at low pH but become somewhat helical at neutral pH. Studies of mixed peptide binding stoichiometry indicate formation of complementary heterooligomers that retain their porphyrin-binding capabilities and produce an additional binding site at their junction. These results have implications for the design of photoelectronically active biomaterials. 2366-PosOptimization of the Site-Identification by Ligand Competitive Saturation (SILCS) as an Accurate and Reliable Technique in Lead Optimization