GPU-optimized approaches to molecular docking-based virtual screening in drug discovery: A comparative analysis

Finding a novel drug is a very long and complex procedure. Using computer simulations, it is possible to accelerate the preliminary phases by performing a virtual screening that filters a large set of drug candidates to a manageable number. This paper presents the implementations and comparative analysis of two GPU-optimized implementations of a virtual screening algorithm targeting novel GPU architectures. This work focuses on the analysis of parallel computation patterns and their mapping onto the target architecture. The first method adopts a traditional approach that spreads the computation for a single molecule across the entire GPU. The second uses a novel batched approach that exploits the parallel architecture of the GPU to evaluate more molecules in parallel. Experimental results showed a different behavior depending on the size of the database to be screened, either reaching a performance plateau sooner or having a more extended initial transient period to achieve a higher throughput (up to 5x), which is more suitable for extreme-scale virtual screening campaigns

An extreme-scale virtual screening platform for drug discovery

Virtual screening is one of the early stages that aims to select a set of promising ligands from a vast chemical library. Molecular Docking is a crucial task in the process of drug discovery and it consists of the estimation of the position of a molecule inside the docking site. In the contest of urgent computing, we designed from scratch the EXSCALATE molecular docking platform to benefit from heterogeneous computation nodes and to avoid scaling issues

MEDIATE - Molecular DockIng at homE: Turning collaborative simulations into therapeutic solutions

IntroductionCollaborative computing has attracted great interest in the possibility of joining the efforts of researchers worldwide. Its relevance has further increased during the pandemic crisis since it allows for the strengthening of scientific collaborations while avoiding physical interactions. Thus, the E4C consortium presents the MEDIATE initiative which invited researchers to contribute via their virtual screening simulations that will be combined with AI-based consensus approaches to provide robust and method-independent predictions. The best compounds will be tested, and the biological results will be shared with the scientific community.Areas coveredIn this paper, the MEDIATE initiative is described. This shares compounds' libraries and protein structures prepared to perform standardized virtual screenings. Preliminary analyses are also reported which provide encouraging results emphasizing the MEDIATE initiative's capacity to identify active compounds.Expert opinionStructure-based virtual screening is well-suited for collaborative projects provided that the participating researchers work on the same input file. Until now, such a strategy was rarely pursued and most initiatives in the field were organized as challenges. The MEDIATE platform is focused on SARS-CoV-2 targets but can be seen as a prototype which can be utilized to perform collaborative virtual screening campaigns in any therapeutic field by sharing the appropriate input files

The role of the profundoplasty in the modern management of patient with peripheral vascular disease

BACKGROUND: The occlusion of superficial femoris artery (SFA) is a common feature in peripheral vascular disease, so the profunda femoris artery (PFA) is a crucial collateral pathway for the perfusion of the lower limb. The purpose of this study is to discuss the safety, clinical, and hemodynamic efficacy of profundoplasty on the basis of limb salvage, patency, and freedom from reintervention rates. Furthermore, this study aims to identify the risk factors linked to the failure of the procedure. METHODS: The study is based on a retrospective analysis of prospectively collected data of identified patients who underwent profundoplasty from March 2005 to October 2015. All patients showed a hemodynamic stenosis, extended from the posterior wall of the common femoral artery (CFA) into the origin of the PFA and concomitant occlusion of SFA. Endarterectomy with patch angioplasty was performed in all cases. In patients with concomitant iliac occlusive disease, a hybrid treatment was carried out to restore an adequate inflow through an endovascular approach. RESULTS: Seventy-four profundoplasty were performed during the study period. Isolate profundoplasty was performed in 56 cases (75.7%), while in the remaining 18 cases (24.3%), concomitant endovascular treatment of iliac lesions was performed. Hemodynamic success was achieved in 90.5% of the cases. The mean ankle-brachial index significantly improved, rising from 0.36 ± 0.17 preoperatively to 0.57 ± 0.20 postoperatively (P < 0.001). The median follow-up period was 33 months. Primary patency rate was 98.5% at 12, 36, and 60 months. Freedom from reintervention rate was 97% at 1 year and 95.3% at 3 and 5 years. Limb salvage rate was 96.9% at 1 year and 92.7% at 3 and 5 years. Survival rates were 86%, 60%, and 47.4% at 1, 3, and 5 years, respectively. Multivariate analysis identified Rutherford class 5 or 6 lesions as the strongest predictors of major amputation or reintervention (odds ratio, 9.37; confidence interval: 0.98-89.27; P = 0.05). CONCLUSIONS: Profundoplasty is a durable, safe, and effective procedure in terms of clinical and hemodynamic results for patients characterized by occlusion of SFA and stenosis of CFA extended to profunda ostium. For patients with Rutherford category 5 and 6 ischemia, the only profundoplasty does not seem to be adequate, and concomitant distal bypass should be necessary to improve limb salvage and decrease reintervention rate

The ANTAREX domain specific language for high performance computing

The ANTAREX project relies on a Domain Specific Language (DSL) based on Aspect Oriented Programming (AOP) concepts to allow applications to enforce extra functional properties such as energy-efficiency and performance and to optimize Quality of Service (QoS) in an adaptive way. The DSL approach allows the definition of energy-efficiency, performance, and adaptivity strategies as well as their enforcement at runtime through application autotuning and resource and power management. In this paper, we present an overview of the key outcome of the project, the ANTAREX DSL, and some of its capabilities through a number of examples, including how the DSL is applied in the context of the project use cases.Web of Science68735

The Indigo System in acute lower-limb malperfusion (INDIAN) registry. Protocol

Background: Acute lower limb ischemia (ALLI) poses a major threat to limb survival. For many years, surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution to the management of ALLI. It seems that the newly designed endovascular thrombectomy devices may shift treatment recommendations toward endovascular options. This protocol study aims to collect evidence supporting the latest hypothesis. Objective: The devices under investigation are the Penumbra/Indigo Systems (Penumbra Inc). The objective of this clinical investigation is to evaluate, in a controlled setting, the early safety and effectiveness of the devices and to define the optimal technique for the use of these systems in patients with confirmed peripheral acute occlusions. Methods: This study will be an interventional prospective trial of patients with a diagnosis of ALLI treated with Penumbra/Indigo devices. This project is intended to be a national platform where every physician invited to participate could register his or her own data procedure. The primary outcome is the technical success of thromboaspiration with the Indigo System. Assessment of vessel patency will be recorded using the Thrombolysis in Myocardial Infarction (TIMI) score classifications before and after use of the device. Clinical success at follow-up is defined as an improvement of Rutherford classification at 1-month follow-up of one class or more as compared to the preprocedure Rutherford classification. Secondary endpoints include the following: (1) safety rate at discharge, defined as the absence of any serious adverse events; (2) primary patency at 1 month, defined as a target lesion without a hemodynamically significant stenosis or reocclusion on duplex ultrasound (&gt;50%) and without target lesion reintervention within 1 month; and (3) limb salvage at 1 month. Results: The study is currently in the recruitment phase and the final patient is expected to be treated by the end of March 2019. A total of 150 patients will be recruited. Analyses will focus on primary and secondary endpoints. Conclusions: These new endovascular thrombectomy devices that are specifically designed for peripheral intervention in this difficult set of patients, as those under investigation in the proposed registry, may offer improved clinical outcomes with lower rates of major systemic and local complications. Following completion of this study, it is expected that the value of the Indigo Thrombectomy System in the treatment of ALLI will be better defined. As a result, a shift of treatment recommendations toward endovascular options may be observed in the near future