BMaps: A Web Application for Fragment-Based Drug Design and Compound Binding Evaluation.

Fragment-based drug design uses data about where, and how strongly, small chemical fragments bind to proteins, to assemble new drug molecules. Over the past decade, we have been successfully using fragment data, derived from thermodynamically rigorous Monte Carlo fragment-protein binding simulations, in dozens of preclinical drug programs. However, this approach has not been available to the broader research community because of the cost and complexity of doing simulations and using design tools. We have developed a web application, called BMaps, to make fragment-based drug design widely available with greatly simplified user interfaces. BMaps provides access to a large repository (>550) of proteins with 100s of precomputed fragment maps, druggable hot spots, and high-quality water maps. Users can also employ their own structures or those from the Protein Data Bank and AlphaFold DB. Multigigabyte data sets are searched to find fragments in bondable orientations, ranked by a binding-free energy metric. The designers use this to select modifications that improve affinity and other properties. BMaps is unique in combining conventional tools such as docking and energy minimization with fragment-based design, in a very easy to use and automated web application. The service is available at https://www.boltzmannmaps.com.

Correlation among scapular asymmetry, neck pain, and neck disability index (NDI) in young women with slight neck pain.

[Purpose] This study aimed to investigate the correlations among scapular asymmetry, neck pain, and neck disability index in women in their 20s with slight neck pain. [Subjects and Methods] A total of 60 female students at U university in Gyeongsangbuk-do, South Korea, participated in this study. The lateral scapular slide test, which measures the distance between the thorax and scapula, was used to analyze the scapular asymmetry. The lateral scapular slide test was performed in three positions. The visual analogue scale and neck disability index were used to measure neck pain. [Results] In the lateral scapular slide test in position 3 (shoulder abduction at 90 degrees), the scapular left-right asymmetry and VAS showed a moderate positive linear relationship, with r=0.344. The VAS and NDI showed a moderate positive linear relationship, with r = 0.632. [Conclusion] Scapular asymmetry indicates imbalance of surrounding muscles of the scapula and is related to neck pain based on the results of measuring the distance from the thorax to the scapula.

Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient-Derived Chips.

Glioblastoma (GBM) is one of the most intractable tumor types due to the progressive drug resistance upon tumor mass expansion. Incremental hypoxia inside the growing tumor mass drives epigenetic drug resistance by activating nongenetic repair of antiapoptotic DNA, which could be impaired by drug treatment. Hence, rescuing intertumor hypoxia by oxygen-generating microparticles may promote susceptibility to antitumor drugs. Moreover, a tumor-on-a-chip model enables user-specified alternation of clinic-derived samples. This study utilizes patient-derived glioblastoma tissue to generate cell spheroids with size variations in a 3D microchannel network chip (GBM chip). As the spheroid size increases, epigenetic drug resistance is promoted with inward hypoxia severance, as supported by the spheroid size-proportional expression of hypoxia-inducible factor-1a in the chip. Loading antihypoxia microparticles onto the spheroid surface significantly reduces drug resistance by silencing the expression of critical epigenetic factor, resulting in significantly decreased cell invasiveness. The results are confirmed in vitro using cell line and patient samples in the chip as well as chip implantation into a hypoxic hindlimb ischemia model in mice, which is an unprecedented approach in the field.