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Additional file 1. Code Snippets regarding DrugTax.

Membrane proteins (MPs) are key players in a variety of different cellular processes and constitute the target of around 60% of all Food and Drug Administration–approved drugs. Despite their importance, there is still a massive lack of relevant structural, biochemical and mechanistic information mainly due to their localization within the lipid bilayer. To help fulfil this gap, we developed the MEmbrane protein dimer Novel Structure Analyser database (MENSAdb). This interactive web application summarizes the evolutionary and physicochemical properties of dimeric MPs to expand the available knowledge on the fundamental principles underlying their formation. Currently, MENSAdb contains features of 167 unique MPs (63% homo- and 37% heterodimers) and brings insights into the conservation of residues, accessible solvent area descriptors, average B-factors, intermolecular contacts at 2.5 Å and 4.0 Å distance cut-offs, hydrophobic contacts, hydrogen bonds, salt bridges, π–π stacking, T-stacking and cation–π interactions. The regular update and organization of all these data into a unique platform will allow a broad community of researchers to collect and analyse a large number of features efficiently, thus facilitating their use in the development of prediction models associated with MPs. Database URL: http://www.moreiralab.com/resources/mensadb.

Structural characterization of proteins and their complexes is a fundamental part in understanding any biological phenomena. Yet, the experimental determination of the three‐dimensional (3D) structure of proteins and their complexes remains a challenging undertaking. In order to complement the experimental approaches, computational methods have been developed based on a variety of algorithms and models to fill the gap between the amount of sequences and structures. In this article, we review the most common methodological approaches currently used in the field, highlighting the ab initio structure prediction methods and methods for the prediction and structural modeling of protein–protein interfaces (PPIs). We particularly focus on the use of evolutionary information to guide the modeling process.

Background Membrane proteins (MPs) play diverse and important functions in living organisms. They constitute 20% to 30% of the known bacterial, archaean and eukaryotic organisms' genomes. In humans, their importance is emphasized as they represent 50% of all known drug targets. Nevertheless, experimental determination of their three-dimensional (3D) structure has proven to be both time consuming and rather expensive, which has led to the development of computational algorithms to complement the available experimental methods and provide valuable insights. Scope of review This review highlights the importance of membrane proteins and how computational methods are capable of overcoming challenges associated with their experimental characterization. It covers various MP structural aspects, such as lipid interactions, allostery, and structure prediction, based on methods such as Molecular Dynamics (MD) and Machine-Learning (ML). Major conclusions Recent developments in algorithms, tools and hybrid approaches, together with the increase in both computational resources and the amount of available data have resulted in increasingly powerful and trustworthy approaches to model MPs. General significance Even though MPs are elementary and important in nature, the determination of their 3D structure has proven to be a challenging endeavor. Computational methods provide a reliable alternative to experimental methods. In this review, we focus on computational techniques to determine the 3D structure of MP and characterize their binding interfaces. We also summarize the most relevant databases and software programs available for the study of MPs.