Protein-Ligand Scoring with Convolutional Neural Networks

Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict binding affinities and poses. The ever-expanding amount of protein-ligand binding and structural data enables the use of deep machine learning techniques for protein-ligand scoring. We describe convolutional neural network (CNN) scoring functions that take as input a comprehensive 3D representation of a protein-ligand interaction. A CNN scoring function automatically learns the key features of protein-ligand interactions that correlate with binding. We train and optimize our CNN scoring functions to discriminate between correct and incorrect binding poses and known binders and non-binders. We find that our CNN scoring function outperforms the AutoDock Vina scoring function when ranking poses both for pose prediction and virtual screening

Adversarial consistency for single domain generalization in medical image segmentation

7R01HL141813-06 - NIH/National Heart, Lung, and Blood Institute; NIH/National Institutes of HealthFirst author draf

Electrical resistance associated with the scattering of optically oriented electrons in n-GaAs

In a bulk GaAs crystal, an unusual magnetoresistance effect, which takes place when a spin-polarized current flows through the sample, was detected. Under conditions of optical pumping of electron spins, an external magnetic field directed along the electric current and perpendicular to the oriented spins decreases the resistance of the material. The phenomenon is due to the spin-dependent scattering of electrons by neutral donors. It was found that the sign of the magnetoresistance does not depend on the sign of the exciting light circular polarization, the effect is even with respect to the sign of the spin polarization of the carriers, which indicates a correlation between the spins of optically oriented free electrons and electrons localized on donors.Comment: 9 pages, 4 figure

Identification of Novel Factors Involved in Modulating Motility of Salmonella enterica Serotype Typhimurium

Salmonella enterica serotype Typhimurium can move through liquid using swimming motility, and across a surface by swarming motility. We generated a library of targeted deletion mutants in Salmonella Typhimurium strain ATCC14028, primarily in genes specific to Salmonella, that we have previously described. In the work presented here, we screened each individual mutant from this library for the ability to move away from the site of inoculation on swimming and swarming motility agar. Mutants in genes previously described as important for motility, such as flgF, motA, cheY are do not move away from the site of inoculation on plates in our screens, validating our approach. Mutants in 130 genes, not previously known to be involved in motility, had altered movement of at least one type, 9 mutants were severely impaired for both types of motility, while 33 mutants appeared defective on swimming motility plates but not swarming motility plates, and 49 mutants had reduced ability to move on swarming agar but not swimming agar. Finally, 39 mutants were determined to be hypermotile in at least one of the types of motility tested. Both mutants that appeared non-motile and hypermotile on plates were assayed for expression levels of FliC and FljB on the bacterial surface and many of them had altered levels of these proteins. The phenotypes we report are the first phenotypes ever assigned to 74 of these open reading frames, as they are annotated as ‘hypothetical genes’ in the Typhimurium genome.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Defined Single-Gene and Multi-Gene Deletion Mutant Collections in Salmonella enterica sv Typhimurium

Artículo de publicación ISIWe constructed two collections of targeted single gene deletion (SGD) mutants and two collections of targeted multi-gene deletion (MGD) mutants in Salmonella enterica sv Typhimurium 14028s. The SGD mutant collections contain (1), 3517 mutants in which a single gene is replaced by a cassette containing a kanamycin resistance (KanR) gene oriented in the sense direction (SGD-K), and (2), 3376 mutants with a chloramphenicol resistance gene (CamR) oriented in the antisense direction (SGD-C). A combined total of 3773 individual genes were deleted across these SGD collections. The MGD collections contain mutants bearing deletions of contiguous regions of three or more genes and include (3), 198 mutants spanning 2543 genes replaced by a KanR cassette (MGD-K), and (4), 251 mutants spanning 2799 genes replaced by a CamR cassette (MGD-C). Overall, 3476 genes were deleted in at least one MGD collection. The collections with different antibiotic markers permit construction of all viable combinations of mutants in the same background. Together, the libraries allow hierarchical screening of MGDs for different phenotypic followed by screening of SGDs within the target MGD regions. The mutants of these collections are stored at BEI Resources (www.beiresources.org) and publicly available

Optimal management of GIST tumors located near the gastroesophageal junction: Case report and review of the literature

Introduction: The safety and oncologic outcome of laparoscopic gastric GIST resection is well established especially for lesions <5 cm in diameter. The optimal management of GIST tumors near the GE junction remains unclear. Methods: We present a case-report of a 4.7 cm GIST tumor near the GE junction managed by endoscopically-assisted laparoscopic wedge resection (EAWR). We present a review of the literature highlighting the various combined laparo-endoscopic techniques available. Results: We used the non-touch lesion-lifting method to laparoscopically resect the GIST tumor under endoscopic guidance. There were no complications and the patient was discharged on postoperative day 3. Conclusions: Endoscopically-assisted laparoscopic wedge resections are feasible and safe for GIST tumors near the GE junction