2D Conformal mapping of protein surfaces: applications to VIsualization and DOCKing software

Project Information

VIDOCK

Grant agreement ID: 640283

DOI

10.3030/640283

Project closed

EC signature date 11 June 2015

Start date 1 July 2015

End date 31 December 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 498 791,25

EU contribution

€ 1 498 791,25

Coordinated by

CONSERVATOIRE NATIONAL DES ARTS ET METIERS
France

Periodic Reporting for period 4 - VIDOCK (2D Conformal mapping of protein surfaces: applications to VIsualization and DOCKing software)

Reporting period: 2020-01-01 to 2021-12-31

Summary of the context and overall objectives of the project

Protein-protein interactions play a crucial role in biological processes such as cellular communication, immune defense, cell-growth or programmed cell death. These interactions occur between the respective surfaces of the proteins involved. The characterization of their shape is thus of major importance.

Different methods have been developed to compare protein subparts but very few methods taking into account the whole protein surfaces are available. In the ViDOCK project, we developed tools using 2-dimensional representations of protein surfaces for protein shape recognition and similarity search and create the new generation of interactive molecular visualization and simulation software.

We developed fast shape similarity search methods applied for protein surfaces (PS4 and PLO3S) and created reference protein shape benchmarking datasets. We also developed cutting edge real-time visualization and interactive simulation software such as VTX (https://vtx.drugdesign.fr) and UDock (http://udock.fr).

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Regarding the 1st objective: We have developed tools for generating 2D protein representations (maps). The surface maps are generated using a two-step procedure: A. The protein surface is projected onto a sphere. B. The sphere is then projected onto a plane which resuls into a map of the surface of the protein. These maps are then used to compare the shape of the proteins.

We published protein shape comparison and retrieval prototypes (PS4, SHREC2017), (PLO3S). The descriptor of the PLO3Smethod is a local surface shape descriptor projected on a unit sphere mapped onto a 2D plane and called Surface Wave Interpolated Maps (SWIM). PLO3S allows to rapidly compare protein surface shapes through local comparisons to filter large protein surfaces datasets in virtual protein structures screening pipelines.

We also developed and conducted community benchmarks for protein shape comparison and retrieval in the3D objects retrieval community within the SHREC challenge (SHREC2017-2021). Our protein shape track attracted numerous participants (up to 25) and was among the most popular within the 3D objects retrieval community.


For the 2nd objective, we developed UDock v2 a usable open-source simulation system based on the Udock engine (Levieux et al, Faraday Discuss 2014; http://udock.fr). We are developing new ways to represent and manipulate multiple 3D objects in real time using methods from the video game industry. This allows biologists and chemists not familiar with molecular visualization software to use them in their own professional environment. UDock v2 allows interactive real-time assembly of multiple proteins and includes a virtual camera which allows a local exploration and visualization of the properties of the interfaces of protein assemblies.

We developed and released VTX, a high performance and usable open source molecular visualization software. VTX includes a cutting edge visualization engine, is compliant to most molecular trajectory and structure file formats, includes the alternate camera systems developed in UDock and is freely available at https:vtx.drugdesign.fr

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We have successfully applied computational geometry tools used in robotics and computer vision to generate 2 Dimensional representation of protein surfaces. The maps are then compared in order to compare the shapes. With this approach, we have unconventionally applied a method initially developed and used for generic shape retrieval (Furniture, faces) in computational structural biology. This fast 2D-based shape comparison methods will allow the ViDOCK team to compare the shapes of all proteins in the Protein Databank. This understanding of the shape similarity between protein structures could provide a better insight on protein partners involved in cellular mechanisms and drugs off-targets responsible for adverse effects. We have developed PLO3S a fast and local protein shape comparison method.

We have developed a new way to interact and visualize objects in a molecular visualization software by using a local user-controlled virtual camera. This representation/manipulation is classical in 3rd person manipulation of a character in video games but has not been used so far in molecular visualization software. Using a local virtual camera as a complement to the classical global camera gives an insight notably of the parts of the system that are difficult to visualize such as the interface between opaque objects (like protein surfaces) or very crowded environments.
With this virtual camera, we unconventionally applied interaction methods from the video game industry which is one of the industrial domains where the quality and the usability of the computer-human interaction is the most critical. All video games with approximate controls or uninformative camera angles ended as industrial failures.

These new representation and interaction methods are included in a visualization and simulation we have provided to the community and that is more easily accessible and usable for non experts in computational structural biology: VTX
VTX is optimized to handle efficiently the big data from High Performance Computing Molecular Dynamics Simulation (HPC MD). It is based on a high-performance 3D engine including cutting-edge computer graphics methods, adapted to molecular scenes, that can handle several million atoms on a standard laptop computer (Figure 1.). It also offers a video game based minimalistic task-oriented GUI to maximize its usability and comfort of use.

In this project, we have successfully and unconventionally applied methods and algorithms routinely used in robotics, computer vision and video game industries into structural bioinformatics.