Delineation of protein-ligand interaction modes is key for rational drug discovery. The availability of complex crystal structures is often limited by the aqueous solubility of the compounds, while lead-like compounds with micromolar affinities normally fall into the NMR intermediate exchange regime, in which severe line broadening to beyond the detection of interfacial resonances limits NMR applications. Here, we developed a new method to retrieve low-populated bound-state H pseudocontact shifts (PCSs) using paramagnetic relaxation dispersion (RD). We evaluated using aH PCS-RD approach in a BRM bromodomain lead-like inhibitor to filter molecular docking poses using multiple intermolecular structural restraints. Considering the universal presence of proton atoms in druglike compounds, our work will have wide application in structure-guided drug discovery even under an extreme condition of NMR intermediate exchange and low aqueous solubility of ligands.

Structural data are available in the PDB under the accession number 5YJ8.

The pedagogical content knowledge (PCK) of teachers influences students’ achievement of the learning outcomes. This study examined teachers’ perceived enactment of PCK in biology. The quantitative survey design was adopted by using a Likert-scale questionnaire consisting of six components of PCK, namely curricular saliency, students’ prior knowledge, what makes the subject easy or difficult, representations, conceptual teaching strategies, and assessment. Data on teachers’ perceived enacted PCK (ePCK) were collected from 54 biology teachers selected from 14 secondary schools in three districts of Lusaka province. The data were analyzed by computing descriptive and inferential statistics using Statistical Package for the Social Sciences (SPSS) software. The findings revealed that: (a) respondents’ perceived ePCK was high (M = 4.29, SD = .37), (b) respondents’ perceived ePCK was not influenced by gender, teaching experience, and type of school, (c) respondents’ perceived ePCK was influenced by their academic qualifications, (d) the component students’ prior knowledge and misconceptions was the most enacted component, and (e) the component what makes the subject easy or difficult was the least enacted component. The results highlight areas in teachers’ PCK that require enhancement. The study recommends using teacher professional development to enhance teachers’ ePCK in the component what makes the subject easy or difficult to understand. Further research may use larger samples and more data sources to increase the validity of the findings.