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VirtualFlow Ants-Ultra-Large Virtual Screenings with Artificial Intelligence Driven Docking Algorithm Based on Ant Colony Optimization.

ABSTRACT: The docking program PLANTS, which is based on ant colony optimization (ACO) algorithm, has many advanced features for molecular docking. Among them are multiple scoring functions, the possibility to model explicit displaceable water molecules, and the inclusion of experimental constraints. Here, we add support of PLANTS to VirtualFlow (VirtualFlow Ants), which adds a valuable method for primary virtual screenings and rescoring procedures. Furthermore, we have added support of ligand libraries in the MOL2 format, as well as on the fly conversion of ligand libraries which are in the PDBQT format to the MOL2 format to endow VirtualFlow Ants with an increased flexibility regarding the ligand libraries. The on the fly conversion is carried out with Open Babel and the program SPORES. We applied VirtualFlow Ants to a test system involving KEAP1 on the Google Cloud up to 128,000 CPUs, and the observed scaling behavior is approximately linear. Furthermore, we have adjusted several central docking parameters of PLANTS (such as the speed parameter or the number of ants) and screened 10 million compounds for each of the 10 resulting docking scenarios. We analyzed their docking scores and average docking times, which are key factors in virtual screenings. The possibility of carrying out ultra-large virtual screening with PLANTS via VirtualFlow Ants opens new avenues in computational drug discovery.

SUBMITTER: Gorgulla C

PROVIDER: S-EPMC8199267 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn-hospital cardiac arrest is a major burden in health care. Although several track-and-trigger systems are used to predict cardiac arrest, they often have unsatisfactory performances. We hypothesized that a deep-learning-based artificial intelligence algorithm (DLA) could effectively predict cardiac arrest using electrocardiography (ECG). We developed and validated a DLA for predicting cardiac arrest using ECG.MethodsWe conducted a retrospective study that included 47,505 ECGs of 25,672 adult patients admitted to two hospitals, who underwent at least one ECG from October 2016 to September 2019. The endpoint was occurrence of cardiac arrest within 24 h from ECG. Using subgroup analyses in patients who were initially classified as non-event, we confirmed the delayed occurrence of cardiac arrest and unexpected intensive care unit transfer over 14 days.ResultsWe used 32,294 ECGs of 10,461 patients and 4483 ECGs of 4483 patients from a hospital were used as development and internal validation data, respectively. Additionally, 10,728 ECGs of 10,728 patients from another hospital were used as external validation data, which confirmed the robustness of the developed DLA. During internal and external validation, the areas under the receiver operating characteristic curves of the DLA in predicting cardiac arrest within 24 h were 0.913 and 0.948, respectively. The high risk group of the DLA showed a significantly higher hazard for delayed cardiac arrest (5.74% vs. 0.33%, P < 0.001) and unexpected intensive care unit transfer (4.23% vs. 0.82%, P < 0.001). A sensitivity map of the DLA displayed the ECG regions used to predict cardiac arrest, with the DLA focused most on the QRS complex.ConclusionsOur DLA successfully predicted cardiac arrest using diverse formats of ECG. The results indicate that cardiac arrest could be screened and predicted not only with a conventional 12-lead ECG, but also with a single-lead ECG using a wearable device that employs our DLA.

Project description:The drug development process is a major challenge in the pharmaceutical industry since it takes a substantial amount of time and money to move through all the phases of developing of a new drug. One extensively used method to minimize the cost and time for the drug development process is computer-aided drug design (CADD). CADD allows better focusing on experiments, which can reduce the time and cost involved in researching new drugs. In this context, structure-based virtual screening (SBVS) is robust and useful and is one of the most promising in silico techniques for drug design. SBVS attempts to predict the best interaction mode between two molecules to form a stable complex, and it uses scoring functions to estimate the force of non-covalent interactions between a ligand and molecular target. Thus, scoring functions are the main reason for the success or failure of SBVS software. Many software programs are used to perform SBVS, and since they use different algorithms, it is possible to obtain different results from different software using the same input. In the last decade, a new technique of SBVS called consensus virtual screening (CVS) has been used in some studies to increase the accuracy of SBVS and to reduce the false positives obtained in these experiments. An indispensable condition to be able to utilize SBVS is the availability of a 3D structure of the target protein. Some virtual databases, such as the Protein Data Bank, have been created to store the 3D structures of molecules. However, sometimes it is not possible to experimentally obtain the 3D structure. In this situation, the homology modeling methodology allows the prediction of the 3D structure of a protein from its amino acid sequence. This review presents an overview of the challenges involved in the use of CADD to perform SBVS, the areas where CADD tools support SBVS, a comparison between the most commonly used tools, and the techniques currently used in an attempt to reduce the time and cost in the drug development process. Finally, the final considerations demonstrate the importance of using SBVS in the drug development process.

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VirtualFlow Ants-Ultra-Large Virtual Screenings with Artificial Intelligence Driven Docking Algorithm Based on Ant Colony Optimization.

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