SSAGES : Software Suite for Advanced General Ensemble Simulations

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike. There is a clear need for software that provides rapid, reliable, and easy access to a wide range of advanced sampling methods and that facilitates implementation of new techniques as they emerge. Here we present SSAGES, a publicly available Software Suite for Advanced General Ensemble Simulations designed to interface with multiple widely used molecular dynamics simulations packages. SSAGES allows facile application of a variety of enhanced sampling techniques—including adaptive biasing force, string methods, and forward flux sampling—that extract meaningful free energy and transition path data from all-atom and coarse-grained simulations. A noteworthy feature of SSAGES is a user-friendly framework that facilitates further development and implementation of new methods and collective variables. In this work, the use of SSAGES is illustrated in the context of simple representative applications involving distinct methods and different collective variables that are available in the current release of the suite. The code may be found at: https://github.com/MICCoM/SSAGES-public

Leveraging Free Energy in Molecular Dynamics: Applications and New Approaches

Free energy is the driving force behind countless processes ranging from the biological to the industrial. Large differences in free energy drive processes forward, while large barriers impede transitions. Accurate determination of these differences and barriers allow researchers to calculate key properties. We begin with such an application. Using free energy methods in molecular dynamics, we characterize a block copolymer that forms micelles via crystallization-driven self-assembly. Through a range of free energy calculations where we determine the relative stability of micelles as a function of size, we calculate the equilibrium size, shape, and stability of these micelles. We then turn our attention to the methodology that powers this kind of analysis: free energy calculations in molecular dynamics. Given that free energy is often the quantity of interest in a system studied via molecular dynamics, the length of time these methods take to estimate the free energy strongly influences the computational cost of the studies. We present two methods that leverage self-regularizing neural networks to very rapidly estimate underlying free energy during a molecular dynamics simulation. The first method builds upon an already successful method, Adaptive Biasing Force (ABF), by better handling the error inherent in its estimates and by providing exploratory bias in unvisited regions. The second method further builds on the first by incorporating the frequency of visits in phase space, in addition to the forces, to the final estimate of the free energy for an even faster, more robust estimate. Finally, we seek to expand the reach of these methods by introducing an easy-to-use, powerful and scalable framework for applying these methods to first principles molecular dynamics, and a hierarchical transfer methodology to rapidly converge such calculations

Dissociation of salts in water under pressure

Salts in water at extreme conditions play a fundamental role in determining the properties of the Earthʼs mantle constituents. Here the authors shed light on ion-water and ion-ion interactions for NaCl dissolved in water at conditions relevant to the Earthʼs upper mantle by molecular dynamics simulations

Surveillance of penicillin resistance of Neisseria meningitidis strains from invasive infections between 2013 and 2018 in Turkey

Basaranoglu, Sevgen Tanir/0000-0002-9416-1512; Emiroglu, Melike/0000-0003-1307-0246WOS: 000513186600001PubMed: 32028863Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. the empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0-18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. the data shows appropriateness of third-generation cephalosporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial

Presepsin: A new marker of catheter related blood stream infections in pediatric patients

Background Catheter related blood stream infections (CRBSI) are mostly preventable hospital-acquired conditions. We aimed to investigate the value of presepsin in detection of CRBSI in hospitalized children. Methods Hospitalized pediatric patients who had clinical suspicion of CRBSI were followed. Results of peripheral blood cultures and blood cultures from central venous catheters, procalcitonin (PCT), C-reactive protein (CRP), total white blood cell (WBC) counts were recorded. Serum samples for presepsin were studied at the same time with the samples of healthy controls. The patients with positive blood cultures were defined as proven CRBSI and with negative cultures as suspected CRBSI. Results Fifty-eight patients and 80 healthy controls were included in the study. Proven CRBSI group consisted of 36 patients (62%) with positive blood cultures and compared with the suspected CRBSI group (n = 22, 36%) with negative culture results. There was no difference between proven and suspected CRBSI groups concerning WBC, PCT, CRP and presepsin. Presepsin was significantly higher in patient groups when compared with healthy controls. The receiver operating characteristic curve area under the curve was 0.98 (%95 CI: 0.97–1) and best cut-off value was 990 pg/ml. Conclusion In hospitalized pediatric patients with CRBSI, presepsin may be a helpful rapid marker in early diagnosis

Streptococcus Mitis/Oralis Causing Blood Stream Infections In Pediatric Patients

Viridans streptococci are still under investigation concerning epidemiology, pathogenesis and clinical presentations. We aimed to investigate the clinical presentations and outcomes of pediatric patients infected with Streptococcus mitis/oralis. Based on the accumulation of bloodstream infections (BSI) caused by S. mitis/oralis in 4 patients in our Hematology and Bone Marrow Transplantation Department at a particular time, a review of the medical and microbiological records of pediatric patients with positive blood cultures for S. mitis/oralis in the entire hospital was performed. In addition, a retrospective case-control study was conducted. Pulsed-field gel electrophoresis of S. mitisloralis in 4 patients displayed unrelatedness of the strains. A total of 53 BSI (42 BSI and 11 catheter-related BSI) were analyzed. Thirty-four percent of patients with BSI caused by S. mitis/oralis had febrile neutropenia. Clinical and microbiological outcomes were favorable and infection-related mortality was not observed. Although not significant, previous antibiotic use and trimethoprim-sulfamethoxazole prophylaxis were more common in the case group. S. mitis/oralis seems likely an important agent in bacteremic children who are particularly neutropenic because of the underlying hematologic and oncologic diseases. Prompt management of infections with appropriate antimicrobials, regarding antibiotic susceptibilities of organisms, may facilitate favorable outcomes.WoSScopu

Hierarchical Coupling of First-Principles Molecular Dynamics with Advanced Sampling Methods

We present a seamless coupling of a suite of codes designed to perform advanced sampling simulations, with a first-principles molecular dynamics (MD) engine. As an illustrative example, we discuss results for the free energy and potential surfaces of the alanine dipeptide obtained using both local and hybrid density functionals (DFT), and we compare them with those of a widely used classical force field, Amber99sb. In our calculations, the efficiency of first-principles MD using hybrid functionals is augmented by hierarchical sampling, where hybrid free energy calculations are initiated using estimates obtained with local functionals. We find that the free energy surfaces obtained from classical and first-principles calculations differ. Compared to DFT results, the classical force field overestimates the internal energy contribution of high free energy states, and it underestimates the entropic contribution along the entire free energy profile. Using the string method, we illustrate how these differences lead to different transition pathways connecting the metastable minima of the alanine dipeptide. In larger peptides, those differences would lead to qualitatively different results for the equilibrium structure and conformation of these molecules