Molecular Dynamics Simulation as a Tool to Identify Mutual Synergistic Folding Proteins

• Published in: International journal of molecular sciences Vol. 24; no. 2; p. 1790
• Main Authors: Magyar, Csaba, Németh, Bálint Zoltán, Cserző, Miklós, Simon, István
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.01.2023; MDPI
• Subjects: Amino acid composition; Atomic structure; Computer applications; Computing time; cooperative two-state unfolding; Datasets; disordered proteins; Folding; Intermediates; Molecular dynamics; Molecular Dynamics Simulation; molecular dynamics simulations; mutual synergistic folding; oligomeric proteins; Peptides; Protein Folding; Protein structure; Proteins; Proteins - chemistry; Quaternary structure; Ratios; Simulation; molecular dynamics simulations; cooperative two-state unfolding; disordered proteins; mutual synergistic folding; oligomeric proteins
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24021790

Mutual synergistic folding (MSF) proteins belong to a recently emerged subclass of disordered proteins, which are disordered in their monomeric forms but become ordered in their oligomeric forms. They can be identified by experimental methods following their unfolding, which happens in a single-step cooperative process, without the presence of stable monomeric intermediates. Only a limited number of experimentally validated MSF proteins are accessible. The amino acid composition of MSF proteins shows high similarity to globular ordered proteins, rather than to disordered ones. However, they have some special structural features, which makes it possible to distinguish them from globular proteins. Even in the possession of their oligomeric three-dimensional structure, classification can only be performed based on unfolding experiments, which are frequently absent. In this work, we demonstrate a simple protocol using molecular dynamics simulations, which is able to indicate that a protein structure belongs to the MSF subclass. The presumption of the known atomic resolution quaternary structure is an obvious limitation of the method, and because of its high computational time requirements, it is not suitable for screening large databases; still, it is a valuable in silico tool for identification of MSF proteins.