Last month, I had the privilege of being invited to the KAUST Research Conference on Computational Advances in Structural Biology, held from May 1-3, 2023. This gave me the opportunity to present some of the latest OPIG works on small molecules while visiting an exceptional campus with state-of-the-art facilities in one of those corners of the world that are not widely known. Moreover, the experience went beyond the impressive surroundings as I had the chance to attend a highly engaging conference and meet many scientists from different backgrounds.

The conference brought together experts in the field to explore cutting-edge developments in computational structural biology. It had a primary focus on advancements in protein structure prediction, multi-scale simulations, and integrative structural biology. Cryo-electron microscopy (cryo-EM) was the most popular experimental technique, with more than a third of the talks dedicated to its applications. These talks showcased impressive examples where structure prediction, simulations, and mid-resolution cryo-EM maps were combined to construct atomic models of large macromolecular complexes.

Notable examples of integrative works were presented by Jan Kosinski and Thomas Miller, among others. Jan Kosinski shared insights into the model of the human nuclear pore complex, highlighting the integration of cryo-electron tomography (cryo-ET), prior experimental knowledge, and AlphaFold predictions. Thomas Miller, on the other hand, presented his work on EM-based visual biochemistry, which combines single-particle cryo-electron microscopy (cryo-EM), and time-resolved experiments, as a tool to study the molecular mechanisms of eukaryotic DNA replication.

There were also several talks about novel algorithms. Nazim Bouatta presented some less-known details about OpenFold and introduced some of their approaches to tackling the problem of multimer modelling. He also announced the future release of folding methods for predicting protein-ligand complexes. Jianlin Cheng presented MULTICOM, their new protein structure predictor based on consensus predictions from Alphafold. Sergei Grudinin showed deep-learning tools able to predict protein dynamics as well as some integrative modelling tools driven by low-resolution experimental observations, such as small-angle scattering.

On the cryo-EM methods side, Mikhail Kudryashev presented TomoBEAR and SUSAN, cryoEM tools developed to automatize the analysis of tomographic data. Johannes Schwab presented dynamight, a deep learning-based approach for heterogeneity analysis in single particle cryo-EM. While, on the ComChem side, Haribabu Arthanari showed their ultra-large Virtual screening platform and Jean-Louis Reymond talked about tools to enumerate, visualize and search the vast chemical space of drug-like molecules

Overall, the conference provided a quite diverse set of talks that facilitated multidisciplinary views and discussions. From protein structure prediction to integrative approaches combining experimental and computational methods, the talks showed the transformative potential of computational analysis in unravelling the complexities of biological macromolecules.

In the age of highly accurate structure prediction methods, I have seen more and more usage of cross-linking mass-spectrometry (XL-MS) and I wanted to understand its limitations more carefully. This is more of a guide to interpreting the data rather than how to perform the experiment.