MDBenchmark: A toolkit to optimize the performance of molecular dynamics simulations

Despite the impending flattening of Moore's law, the system size, complexity, and length of molecular dynamics (MD) simulations keep on increasing, thanks to effective code parallelization and optimization combined with algorithmic developments. Going forward, exascale computing poses new challenges to the efficient execution and management of MD simulations. The diversity and rapid developments of hardware architectures, software environments, and MD engines make it necessary that users can easily run benchmarks to optimally set up simulations, both with respect to time-to-solution and overall efficiency. To this end, we have developed the software MDBenchmark to streamline the setup, submission, and analysis of simulation benchmarks and scaling studies. The software design is open and as such not restricted to any specific MD engine or job queuing system. To illustrate the necessity and benefits of running benchmarks and the capabilities of MDBenchmark, we measure the performance of a diverse set of 23 MD simulation systems using GROMACS 2018. We compare the scaling of simulations with the number of nodes for central processing unit (CPU)-only and mixed CPU-graphics processing unit (GPU) nodes and study the performance that can be achieved when running multiple simulations on a single node. In all these cases, we optimize the numbers of message passing interface (MPI) ranks and open multi-processing (OpenMP) threads, which is crucial to maximizing performance. Our results demonstrate the importance of benchmarking for finding the optimal system and hardware specific simulation parameters. Running MD simulations with optimized settings leads to a significant performance increase that reduces the monetary, energetic, and environmental costs of MD simulations

Health beliefs before and after participation on an exercised-based rehabilitation programme for chronic knee pain: doing is believing

BACKGROUND: To explore the health beliefs, experiences, treatment and expectations of people with chronic knee pain, and investigate if, how and why these change after taking part on an integrated exercise-based rehabilitation programme--Enabling Self-management and Coping with Arthritis knee Pain through Exercise, ESCAPE-knee pain. METHODS: Semi-structured interviews were conducted with people with chronic knee pain, before (n=29) and after (n=23) participation on the programme. Thematic analysis was used to document people's baseline health beliefs, attitudes and cognitions, and to see if how and why these changed after completing the programme. RESULTS: Initially people had poor understanding and negative, fatalistic beliefs about the management or prognosis for knee pain. Following the programme the majority of participants had positive experiences describing improvement in pain, physical and psychosocial functioning, greater knowledge and understanding of their condition and treatment options, and in their ability to use exercise to control symptoms. Beliefs about the causation and prognosis of knee pain were unchanged, but their concerns about possible dangers of exercise had decreased, they appreciated how exercise could reduce symptoms (treatment beliefs) and their confidence in their ability to use exercise to effect improvements (exercise self-efficacy) increased. These improvements were attributed to the content and structure of the programme, and the care and guidance of the physiotherapist. Several expressed a need for on-going support. CONCLUSIONS: ESCAPE-knee pain appears to achieve improvements by increasing people's treatment belief in safety and the utility of exercise to control symptoms, rather than alteration in their beliefs about causation or prognosis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN94658828

Osh proteins control nanoscale lipid organization necessary for PI(4,5)P2 synthesis

The plasma membrane (PM) is composed of a complex lipid mixture that forms heterogeneous membrane environments. Yet, how small-scale lipid organization controls physiological events at the PM remains largely unknown. Here, we show that ORP-related Osh lipid exchange proteins are critical for the synthesis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2], a key regulator of dynamic events at the PM. In real-time assays, we find that unsaturated phosphatidylserine (PS) and sterols, both Osh protein ligands, synergistically stimulate phosphatidylinositol 4-phosphate 5-kinase (PIP5K) activity. Biophysical FRET analyses suggest an unconventional co-distribution of unsaturated PS and phosphatidylinositol 4-phosphate (PI4P) species in sterol-containing membrane bilayers. Moreover, using in vivo imaging approaches and molecular dynamics simulations, we show that Osh protein-mediated unsaturated PI4P and PS membrane lipid organization is sensed by the PIP5K specificity loop. Thus, ORP family members create a nanoscale membrane lipid environment that drives PIP5K activity and PI(4,5)P2 synthesis that ultimately controls global PM organization and dynamics