ľ¹Ï¸£ÀûÓ°ÊÓ

The main biomolecules of life, namely proteins, nucleic acids, carbohydrates and lipids, often function by binding one to another. Over the recent years, computational structural biology has gained importance to understand the underlying mechanisms of biomolecular interactions, for which a variety of computational models have been developed. Docking has been consolidated as one of the most popular computational methods for studying biomolecularassociation and has been applied to a wide range of systems. Furthermore, the docking field is increasingly making use of experimental information for improving the predictions. This, broadly known as integrative modeling, is a powerful approach to determine structures of biological systems by a combination of experimental and theoretical methods.

This thesis deals with three main topics, not in order of appearance: (1) Coarse-grained and hybrid approaches for the integrative modeling of large protein protein and protein-nucleic acid complexes (Chapters 1, 3 and 4), (2) the use of experimental information in docking calculations with LightDock10, another docking software (Chapter 2), and (3) the integrative modeling of membrane-associated protein assemblies combining LightDock and HADDOCK (Chapter 5).

Chapter 1 provides a review of several representative coarse-grained/hybrid approaches and parametrization strategies for the modeling of biomolecular complexes. Chapter 2 describes the implementation and use of experimental information into the LightDock docking software. Chapter 3 details the implementation of a coarse-grained docking protocol for protein-protein complexes into the information-driven software HADDOCK, based on the MARTINI coarse-grained force field, and Chapter 4 its extension to nucleic acids, including specific considerations to account for Watson-Crick interactions. The final chapter of this thesis, Chapter 5, combines various of the developments described in Chapters 2 and 3 into a novel protocol for the integrative modeling of membrane-associated protein assemblies, which are notoriously challenging to characterize experimentally and have received little attention so far. The thesis ends with a Conclusions and Perspectives section.