phenix.mr_rosetta: molecular replacement and model rebuilding with Phenix and Rosetta.

The combination of algorithms from the structure-modeling field with those of crystallographic structure determination can broaden the range of templates that are useful for structure determination by the method of molecular replacement. Automated tools in phenix.mr_rosetta simplify the application of these combined approaches by integrating Phenix crystallographic algorithms and Rosetta structure-modeling algorithms and by systematically generating and evaluating models with a combination of these methods. The phenix.mr_rosetta algorithms can be used to automatically determine challenging structures. The approaches used in phenix.mr_rosetta are described along with examples that show roles that structure-modeling can play in molecular replacement

IDSS: deformation invariant signatures for molecular shape comparison

<p>Abstract</p> <p>Background</p> <p>Many molecules of interest are flexible and undergo significant shape deformation as part of their function, but most existing methods of molecular shape comparison (MSC) treat them as rigid bodies, which may lead to incorrect measure of the shape similarity of flexible molecules.</p> <p>Results</p> <p>To address the issue we introduce a new shape descriptor, called Inner Distance Shape Signature (IDSS), for describing the 3D shapes of flexible molecules. The inner distance is defined as the length of the shortest path between landmark points within the molecular shape, and it reflects well the molecular structure and deformation without explicit decomposition. Our IDSS is stored as a histogram which is a probability distribution of inner distances between all sample point pairs on the molecular surface. We show that IDSS is insensitive to shape deformation of flexible molecules and more effective at capturing molecular structures than traditional shape descriptors. Our approach reduces the 3D shape comparison problem of flexible molecules to the comparison of IDSS histograms.</p> <p>Conclusion</p> <p>The proposed algorithm is robust and does not require any prior knowledge of the flexible regions. We demonstrate the effectiveness of IDSS within a molecular search engine application for a benchmark containing abundant conformational changes of molecules. Such comparisons in several thousands per second can be carried out. The presented IDSS method can be considered as an alternative and complementary tool for the existing methods for rigid MSC. The binary executable program for Windows platform and database are available from <url>https://engineering.purdue.edu/PRECISE/IDSS</url>.</p

Microbiological Diagnosis and Antibiotic Therapy in Patients with Community-Acquired Pneumonia and Acute COPD Exacerbation in Daily Clinical Practice: Comparison to Current Guidelines

Background: The aim of this secondary analysis was to evaluate current microbiological approaches, microbiology, and antibiotic therapy in patients with community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in clinical practice and to compare them with current international guidelines. Methods: A total of 362 patients with suspected CAP were enrolled in 14 European centers in a prospective multicenter study. Results: A total of 279 inpatients (CAP, n = 222; AECOPD, n = 57) were evaluated. A total of 83 (37 %) CAP patients and 25 (44 %) AECOPD patients did not undergo any microbiological tests. In patients with CAP/AECOPD, blood culture was performed in 109 (49 %)/16 (28.1 %), urinary antigen tests for Legionella pneumophila in 67 (30 %)/9 (16 %), and sputum investigation in 55 (25 %)/17 (30 %), respectively. The most frequent pathogens in CAP were Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, L. pneumophila, Staphylococcus aureus, and Enterobacter cloacae; in AECOPD they were Escherichia coli, Haemophilus haemolyticus, Haemophilus influenzae, and Moraxella catarrhalis. All CAP patients (mean = 11.1 days) and 35 (61.4 %) of AECOPD patients (mean = 8.9 days) received antibiotics. CAP patients were given mostly aminopenicillin with β-lactamase inhibitors and AECOPD patients were given mostly cephalosporins. Conclusions: Pathogens isolated in CAP and AECOPD and the antibiotic therapy used are in good accordance with the guidelines. Blood culture, recommended for all CAP patients, was performed in only 50 % of the cases and antibiotic therapy lasted longer than the suggested 5-7 days. Therefore, international guidelines regarding performance of blood culture and duration of antibiotic therapy should be adopted more often. This duration was independent of the number of isolated pathogens and number of symptoms on admission. Therefore, the question arises as to whether microbiological data are necessary only for patients who are resistant to initial therapy

Rules and Tools in the Battle against Superbugs - A call for integrated strategies and enhanced international collaboration to promote antimicrobial drug development

The lack of treatments during the recent Ebola and Zika outbreaks dramatically exposed the vulnerability of the global health system and the dire consequences thereof. But even where therapies against infectious diseases had been available, an additional threat has gained world-wide attention: antimicrobial resistance (AMR). A growing number of microbial organisms are becoming resistant to available drugs with increasingly diverse risks for a rapid global spreading of infections. Unfortunately, the traditional IP based innovation system and regulatory frameworks do not provide sufficient incentives to invest in the development of new antimicrobials. Hence, there are few new treatments in the pipeline to replace a growing number of ineffective drugs or problematic drug combinations. Repairing these broken economic incentives, improving access to and sustaining the effectiveness of antimicrobials is among the most important challenges in the health and life sciences. In this paper we emphasize that this goal can only be achieved through integrated strategies and a better global coordination of interdisciplinary multi-sector responses