The SwissSimilarity 2021 Web Tool: Novel Chemical Libraries and Additional Methods for an Enhanced Ligand-Based Virtual Screening Experience

Hit finding, scaffold hopping, and structure–activity relationship studies are important tasks in rational drug discovery. Implementation of these tasks strongly depends on the availability of compounds similar to a known bioactive molecule. SwissSimilarity is a web tool for low-to-high-throughput virtual screening of multiple chemical libraries to find molecules similar to a compound of interest. According to the similarity principle, the output list of molecules generated by SwissSimilarity is expected to be enriched in compounds that are likely to share common protein targets with the query molecule and that can, therefore, be acquired and tested experimentally in priority. Compound libraries available for screening using SwissSimilarity include approved drugs, clinical candidates, known bioactive molecules, commercially available and synthetically accessible compounds. The first version of SwissSimilarity launched in 2015 made use of various 2D and 3D molecular descriptors, including path-based FP2 fingerprints and ElectroShape vectors. However, during the last few years, new fingerprinting methods for molecular description have been developed or have become popular. Here we would like to announce the launch of the new version of the SwissSimilarity web tool, which features additional 2D and 3D methods for estimation of molecular similarity: extended-connectivity, MinHash, 2D pharmacophore, extended reduced graph, and extended 3D fingerprints. Moreover, it is now possible to screen for molecular structures having the same scaffold as the query compound. Additionally, all compound libraries available for screening in SwissSimilarity have been updated, and several new ones have been added to the list. Finally, the interface of the website has been comprehensively rebuilt to provide a better user experience. The new version of SwissSimilarity is freely available starting from December 2021.

Comparing Two Different Automatic Methods to Measure Femoral Neck-Shaft Angle Based on PointNet++ Network

Bacnground: Accurate measurement of the femoral neck-shaft angle (NSA) is of great significance for diagnosing hip joint diseases and preoperative planning of total hip arthroplasty. However, the fitting lines of the femoral neck and femoral shaft did not always intersect in 3D space. Thus, it is unclear whether there is a difference between 2D and 3D methods for measuring NSA. Methods: The femoral point cloud datasets from 310 subjects were segmented into three regions, including the femoral head, femoral neck, and femoral shaft using PointNet++. We created a projection plane to simulate the hip anteroposterior radiograph and fitted the femoral neck axis and femoral shaft axis to complete the 2D measurement, while we directly fitted the two axes in space to complete the 3D measurement. Also, we conducted the manual measurement of the NSA. We verified the accuracy of the segmentation and compared the results of the two automatic and manual methods. Results: The Dice coefficient of femoral segmentation reached 0.9746, and MIoU of that was 0.9165. No significant difference was found between any two of the three methods. While comparing the 2D and 3D methods, the average accuracy was 98.00%, and the average error was 2.58°. Conclusion: This paper proposed two accurate and automatic methods to measure the NSA based on a 2D plane and a 3D model respectively. Although the femoral neck and femoral shaft axes did not intersect in 3D space, the NSAs obtained by 2D and 3D methods were basically consistent.

Enhancing 3D Models with Urban Information: A Case Study Involving Local Authorities and Property Professionals in New Zealand: Quantifying the Benefit of 3D over Alternative 2D systems

<p>This thesis aimed to reach two principal outcomes: To develop a robust testing methodology that allowed a detailed and fair comparative analysis of the benefit, or otherwise, of 3D methods of information interrogation over alternative 2D methods; and to test the ability for a single model to have multiple user-group functionality. The research used the examples of two user-groups within the urban planning industry and their typical decision making processes. A robust testing methodology was developed to investigate the usefulness of 3D in a detailed and focused manner involving individual end-users as participants in a case study. The development of this efficient process assisted the study in moving past the initial visual impact of the models. The method employed a combination of three research instruments: A focus group formed the base from which an urban planning task, questionnaire and guided discussion investigated evidence for the benefit or otherwise of 3D using both quantitative and subjective measures. Two widely disparate user-groups were selected to further test the functionality of a resource to meet the needs of multiple users: city council urban designers and property developers. The research revealed that 3D methods of information visualisation allow users to develop a greater spatial awareness, increasing their understanding of information, when compared to alternative 2D methods. While evidence for this benefit was established using both quantitative and subjective methods, the research proved that this increased understanding does not necessarily lead to quicker decisions as the 2D group completed the task faster and more accurately than the 3D group. The ability for a single model to have multiple user-group functionality was confirmed as each of two disparate user-groups noted that the availability of the other user-group's information was of positive benefit to their understanding of the proposed development within the urban planning task.</p>

Enhancing 3D Models with Urban Information: A Case Study Involving Local Authorities and Property Professionals in New Zealand: Quantifying the Benefit of 3D over Alternative 2D systems

<p>This thesis aimed to reach two principal outcomes: To develop a robust testing methodology that allowed a detailed and fair comparative analysis of the benefit, or otherwise, of 3D methods of information interrogation over alternative 2D methods; and to test the ability for a single model to have multiple user-group functionality. The research used the examples of two user-groups within the urban planning industry and their typical decision making processes. A robust testing methodology was developed to investigate the usefulness of 3D in a detailed and focused manner involving individual end-users as participants in a case study. The development of this efficient process assisted the study in moving past the initial visual impact of the models. The method employed a combination of three research instruments: A focus group formed the base from which an urban planning task, questionnaire and guided discussion investigated evidence for the benefit or otherwise of 3D using both quantitative and subjective measures. Two widely disparate user-groups were selected to further test the functionality of a resource to meet the needs of multiple users: city council urban designers and property developers. The research revealed that 3D methods of information visualisation allow users to develop a greater spatial awareness, increasing their understanding of information, when compared to alternative 2D methods. While evidence for this benefit was established using both quantitative and subjective methods, the research proved that this increased understanding does not necessarily lead to quicker decisions as the 2D group completed the task faster and more accurately than the 3D group. The ability for a single model to have multiple user-group functionality was confirmed as each of two disparate user-groups noted that the availability of the other user-group's information was of positive benefit to their understanding of the proposed development within the urban planning task.</p>

Explore3DM—A Directory and More for 3D Metrology

Explore3DM will be an online resource to explore the diverse interests behind three-dimensional measurement and three-dimensional metrology (3DM). The motivation has been the development of large-volume and portable 3D methods and systems for applications in manufacturing, an activity which has been growing for the past 40 years. However, the measurement spectrum in Explore3DM will be wider and include, for example, as-built process plant at the large-object end and X-Ray CT inspection at the small-object end. This wider spectrum will support cross-sector research at University College London (UCL) to transfer 3DM developments from one sector to another. Initially, Explore3DM will have a core directory incorporating systems manufacturers, service suppliers, research groups and disseminators of metrology knowledge. Mechanisms for solving end users’ measurement tasks will add to further growth of 3DM. The resource is intended to be free to use and the directory free to join at a basic level. Premium directory sponsorship by commercial companies is expected to provide revenue to sustain and develop the resource and support 3DM development. With regard to standards, LVM and PCM systems and techniques can be difficult to assess with a standardized approach because of the highly flexible ways they can be applied. However, some standards have been developed and there is scope for more, for example in the terminology used. A dictionary will be a component of Explore3DM’s future knowledge base. By presenting a first version in a centralized resource, standardized terminology will be encouraged.

Rapid Identification of Potential Drug Candidates from Multi-Million Compounds’ Repositories. Combination of 2D Similarity Search with 3D Ligand/Structure Based Methods and In Vitro Screening

Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost-effective approach in early drug discovery. If structures of active compounds are available, rapid 2D similarity search can be performed on multimillion compounds’ databases. This approach can be combined with physico-chemical parameter and diversity filtering, bioisosteric replacements, and fragment-based approaches for performing a first round biological screening. Our objectives were to investigate the combination of 2D similarity search with various 3D ligand and structure-based methods for hit expansion and validation, in order to increase the hit rate and novelty. In the present account, six case studies are described and the efficiency of mixing is evaluated. While sequentially combined 2D/3D similarity approach increases the hit rate significantly, sequential combination of 2D similarity with pharmacophore model or 3D docking enriched the resulting focused library with novel chemotypes. Parallel integrated approaches allowed the comparison of the various 2D and 3D methods and revealed that 2D similarity-based and 3D ligand and structure-based techniques are often complementary, and their combinations represent a powerful synergy. Finally, the lessons we learnt including the advantages and pitfalls of the described approaches are discussed.

Efficiency is Doing Things Right: High Throughput, Automated, 3D Methods in the Modern Era of Otolith Morphometrics

The morphometrics of fish otoliths have been commonly used to investigate population structures and the environmental impacts on ontogeny. These studies can require hundreds if not thousands of otoliths to be collected and processed. Processing these otoliths takes up valuable time, money, and resources that can be saved by automation. These structures also contain relevant information in three dimensions that is lost with 2D morphometric methods from photographic analysis. In this study, the otoliths of three populations of Coho Salmon (Oncorhynchus kisutch) were examined with manual 2D, automated 2D, and automated 3D otolith measurement methods. The automated 3D method was able to detect an 8% difference in average otolith density, while 2D methods could not. Due to the loss of information in the z-axis, and the longer processing time, 2D methods can take up to 100 times longer to reach the same statistical power as automated 3D methods. Automated 3D methods are faster, can answer a wider range of questions, and allow fisheries scientists to automate rather monotonous tasks.

Multi-method 2D and 3D reconstruction of gold grains morphology in alluvial deposits: a review and application to the Rivière du Moulin (Québec, Canada)

The aim of this paper is to document and compare the 2D qualitative and semi-quantitative methods currently used to describe the shape of gold grains in fluvial environment to 3D quantitative methods using microtomography and SEM photogrammetry. These 3D methods are used to compute flatness, roundness, convexity, sphericity, and ellipticity shape descriptors of 13 gold grains from the Rivière du Moulin (Québec, Canada) in order to quantify the morphological change along 9 km of fluvial transport. Gold grains have moderate to high values of flatness, compactness, sphericity, and ellipticity indices that do not change significantly with distance of transport, whereas the roundness increases during transport. Gold grains are used to compare 2D and 3D methods and the results show small differences (< 8%) when shape descriptors are computed using image analysis software, whereas the difference (up to 70%) is more important for 2D measurements performed by a human operator. For application and characterization on a large set of gold grains, the 2D methods offer the advantage of speed, whereas, for a more detailed study on a limited number of gold grains, 3D methods enable estimation of the volume and yield more detailed shape descriptors changes during fluvial transport.