Biology subjects

Akulov, V.

Publications and source records attributed to Akulov, V..

3 recordsLinked to original sources

bioRxiv2026

Topological Investigation of Protein Folding and Intrinsic Disorder

Mapping protein conformations into a space of fold topologies offers an unprecedented perspective on the long-standing protein folding problem. In this study, we apply circuit topology to investigate the folding landscape of both stably folded and intrinsically disordered proteins. This topological approach quantifies intra-chain contact arrangements within a polypeptide chain. We demonstrate that ordered and disordered proteins can be distinguished by their topological organization, and that a topology-based model can predict chain compaction and folding state. Furthermore, topology relates to folding and unfolding kinetics and thermodynamics. These findings establish topology as a fundamental concept for understanding protein folding and disorder.

biophysics↗

bioRxiv2025

PyMOL plugin for Protein Circuit Topology

Circuit Topology (CT) provides a fundamental framework for analysing folded polymer chains, with applications in functional annotation, protein engineering and drug development. We present a protein CT analysis plugin for PyMOL v3.1.6.1 with a graphical user interface (GUI), automatic installation, and novel features developed through integration with PyMOL's application programming interface (API). The plugin integrates various previously developed CT methodologies for studying structured proteins and their complexes as well as the dynamics of disordered proteins. Analysis of a representative protein and a molecular dynamics trajectory demonstrates the plugin's three analysis modes and their outputs. The plugin reproduces the reference ProteinCT implementation exactly on the structures tested, and is distributed with a versioned release, a pinned environment and a one-command reproduction of every result reported here.

bioinformatics↗

bioRxiv2024

Phosphorylation regulated conformational diversity and topological dynamics of an intrinsically disordered nuclear receptor

Site-specific phosphorylation of disordered proteins is often considered as a marker of protein activity, yet it is unclear how phosphorylation alters conformational dynamics of disordered protein chains, such as those in the nuclear receptor superfamily. In the case of disordered human glucocorticoid receptor N-terminal domain (GR NTD), a negatively charged region known as core activation function 1 (AF1c) features three phosphorylation sites, regulating its function and intracellular localization. Deletion of this sequence reduces GR transcriptional activation ability dramatically in cell experiments. By developing a circuit topology-based fold analysis approach, combined with atomistic simulations, we reveal that site-specific phosphorylation facilitates formation of non-local contacts, leading to the emergence of disordered compact topologies with significant entanglement, which are distinct from solvent exposed topologies. While we observe that the topological buildup of solvent-exposed states is similar in different phosphovariants, it depends on the exact phosphorylation site for the disordered compact states. This study thus reveals the complex regulatory role of the GR phosphorylation and introduces a unique analysis framework that can be broadly applied to studying topological dynamics of disordered proteins.

biophysics↗