EXCOGITO, an Extensible Coarse-Graining Toolbox for the Investigation of Biomolecules by Means of Low-Resolution Representations.

Bottom-up coarse-grained (CG) models proved to be essential to complement and sometimes even replace all-atom representations of soft matter systems and biological macromolecules. The development of low-resolution models takes the moves from the reduction of the degrees of freedom employed, that is, the definition of a mapping between a system's high-resolution description and its simplified counterpart. Even in the absence of an explicit parametrization and simulation of a CG model, the observation of the atomistic system in simpler terms can be informative: this idea is leveraged by the mapping entropy, a measure of the information loss inherent to the process of coarsening. Mapping entropy lies at the heart of the extensible coarse-graining toolbox, EXCOGITO, developed to perform a number of operations and analyses on molecular systems pivoting around the properties of mappings. EXCOGITO can process an all-atom trajectory to compute the mapping entropy, identify the mapping that minimizes it, and establish quantitative relations between a low-resolution representation and the geometrical, structural, and energetic features of the system. Here, the software, which is available free of charge under an open-source license, is presented and showcased to introduce potential users to its capabilities and usage.

ARCTIC-3D: automatic retrieval and clustering of interfaces in complexes from 3D structural information.

The formation of a stable complex between proteins lies at the core of a wide variety of biological processes and has been the focus of countless experiments. The huge amount of information contained in the protein structural interactome in the Protein Data Bank can now be used to characterise and classify the existing biological interfaces. We here introduce ARCTIC-3D, a fast and user-friendly data mining and clustering software to retrieve data and rationalise the interface information associated with the protein input data. We demonstrate its use by various examples ranging from showing the increased interaction complexity of eukaryotic proteins, 20% of which on average have more than 3 different interfaces compared to only 10% for prokaryotes, to associating different functions to different interfaces. In the context of modelling biomolecular assemblies, we introduce the concept of "recognition entropy", related to the number of possible interfaces of the components of a protein-protein complex, which we demonstrate to correlate with the modelling difficulty in classical docking approaches. The identified interface clusters can also be used to generate various combinations of interface-specific restraints for integrative modelling. The ARCTIC-3D software is freely available at github.com/haddocking/arctic3d and can be accessed as a web-service at wenmr.science.uu.nl/arctic3d.

The HADDOCK2.4 web server for integrative modeling of biomolecular complexes.

Interactions between macromolecules, such as proteins and nucleic acids, are essential for cellular functions. Experimental methods can fail to provide all the information required to fully model biomolecular complexes at atomic resolution, particularly for large and heterogeneous assemblies. Integrative computational approaches have, therefore, gained popularity, complementing traditional experimental methods in structural biology. Here, we introduce HADDOCK2.4, an integrative modeling platform, and its updated web interface ( https://wenmr.science.uu.nl/haddock2.4 ). The platform seamlessly integrates diverse experimental and theoretical data to generate high-quality models of macromolecular complexes. The user-friendly web server offers automated parameter settings, access to distributed computing resources, and pre- and post-processing steps that enhance the user experience. To present the web server's various interfaces and features, we demonstrate two different applications: (i) we predict the structure of an antibody-antigen complex by using NMR data for the antigen and knowledge of the hypervariable loops for the antibody, and (ii) we perform coarse-grained modeling of PRC1 with a nucleosome particle guided by mutagenesis and functional data. The described protocols require some basic familiarity with molecular modeling and the Linux command shell. This new version of our widely used HADDOCK web server allows structural biologists and non-experts to explore intricate macromolecular assemblies encompassing various molecule types.