Bioexcel webinar: Conformational ensembles of intrinsically disordered regions and proteins

Date: May 26th, 2026, 15:00 CEST / 16:00 EEST

Intrinsically disordered proteins and regions (collectively IDRs) are pervasive across proteomes in all kingdoms of life, help shape biological functions, and are involved in numerous diseases [1]. IDRs populate a diverse set of transiently formed structures yet defy commonly held sequence-structure-function relationships [1–3]. Recent developments in protein structure prediction have led to the ability to predict the three-dimensional structures of folded proteins at the proteome scale and have enabled large-scale studies of structure-function relationships. In contrast, knowledge of the conformational properties of fully disordered proteins and long disordered linkers is scarce, in part because the sequences of disordered proteins are poorly conserved and because only few have been characterized experimentally. In my talk I will describe how we can use molecular simulations with coarse-grained models and machine learning to study the relationship between sequence, conformational properties, and functions of IDRs [3].

First, I will describe how we have used experimental data on more than 100 proteins to learn a coarse-grained molecular energy function to predict conformational properties of IDRs [4,5]. By globally optimizing a transferable model, called CALVADOS, we can study the conformational ensemble of an IDR [5,6], multidomain protein [7] and IDRs interacting with disordered RNA [8]. I will describe the Bayesian formalism we developed to parameterize CALVADOS by targeting experimental data, and how this model enables us to study interactions within and between IDRs in biomolecular condensates [6–9].

Second, I will describe how CALVADOS makes it possible to perform large-scale simulations to explore the relationship between sequence, structure, and function of IDRs. I will describe how we have generated conformational ensembles of all intrinsically disordered regions of the human proteome and used these to provide insight into sequence-ensemble relationships and evolutionary conservation of IDR properties [10].

Third, I will describe how we can integrate AlphaFold with CALVADOS to generate conformational ensembles of proteins with both folded and disordered regions, how we benchmarked the method using data for hundreds of proteins, and how the speed and scalability enables us to construct conformational ensembles at the proteome level [11].

See references on main Bioexcel webinar page.

Speakers: Kresten Lindorff-Larsen

Duration: 1 Hour

Webinar will be hosted on ZOOM (install the latest Zoom application before the webinar)