MFIB 2.0: a major update of the database of protein complexes formed by mutual folding of the constituting protein chains.

While the majority of proteins with available structures are able to fold independently and mediate interactions only after acquiring their folded state, a subset of the known protein complexes contains protein chains that are intrinsically disordered in isolation. The Mutual Folding Induced by Binding (MFIB) database collects and classifies protein complexes, wherein all constituent protein chains would be unstable/disordered in isolation but fold into a well-defined 3D complex structure upon binding. This phenomenon is often termed as cooperative folding and binding or mutual synergistic folding (MSF).

Correction: Cserző et al. The First Quarter Century of the Dense Alignment Surface Transmembrane Prediction Method. 2023, , 14016.

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The First Quarter Century of the Dense Alignment Surface Transmembrane Prediction Method.

The dense alignment surface (DAS) transmembrane (TM) prediction method was first published more than 25 years ago. DAS was the one of the earliest tools to discriminate TM proteins from globular ones and to predict the sequence positions of TM helices in proteins with high accuracy from their amino acid sequence alone. The algorithmic improvements that followed in 2002 (DAS-TMfilter) made it one of the best performing tools among those relying on local sequence information for TM prediction.

Palatal asymmetry assessed by intraoral scans: effects of sex, orthodontic treatment, and twinning. A retrospective cohort study.

Background: Symmetry is critical in perceived attractiveness, especially in female faces. The palate determines the teeth' alignment and supports facial soft tissues. Therefore, the study aimed to assess the effects of sex, orthodontic treatment, age, and heritability on the directional, anti-, and fluctuational asymmetry in the digital palatal model.

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

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.

Assortment of Frontiers in Protein Science.

Recent decades have brought significant changes to the protein structure research field [...

Origin of Increased Solvent Accessibility of Peptide Bonds in Mutual Synergetic Folding Proteins.

Mutual Synergetic Folding (MSF) proteins belong to a recently discovered class of proteins. These proteins are disordered in their monomeric but ordered in their oligomeric forms. Their amino acid composition is more similar to globular proteins than to disordered ones.

Macromolecular Interactions of Disordered Proteins.

Proteins are social beings [...

Sequence and Structure Properties Uncover the Natural Classification of Protein Complexes Formed by Intrinsically Disordered Proteins via Mutual Synergistic Folding.

Intrinsically disordered proteins mediate crucial biological functions through their interactions with other proteins. Mutual synergistic folding (MSF) occurs when all interacting proteins are disordered, folding into a stable structure in the course of the complex formation. In these cases, the folding and binding processes occur in parallel, lending the resulting structures uniquely heterogeneous features.

Analysis of Heterodimeric "Mutual Synergistic Folding"-Complexes.

Several intrinsically disordered proteins (IDPs) are capable to adopt stable structures without interacting with a folded partner. When the folding of all interacting partners happens at the same time, coupled with the interaction in a synergistic manner, the process is called Mutual Synergistic Folding (MSF). These complexes represent a discrete subset of IDPs.

Sequential, Structural and Functional Properties of Protein Complexes Are Defined by How Folding and Binding Intertwine.

Intrinsically disordered proteins (IDPs) fulfill critical biological roles without having the potential to fold on their own. While lacking inherent structure, the majority of IDPs do reach a folded state via interaction with a protein partner, presenting a deep entanglement of the folding and binding processes. Protein disorder has been recognized as a major determinant in several properties of proteins, such as sequence, adopted structure upon binding and function.

Physical Background of the Disordered Nature of "Mutual Synergetic Folding" Proteins.

Intrinsically disordered proteins (IDPs) lack a well-defined 3D structure. Their disordered nature enables them to interact with several other proteins and to fulfil their vital biological roles, in most cases after coupled folding and binding. In this paper, we analyze IDPs involved in a new mechanism, mutual synergistic folding (MSF).

DIBS: a repository of disordered binding sites mediating interactions with ordered proteins.

Motivation: Intrinsically Disordered Proteins (IDPs) mediate crucial protein-protein interactions, most notably in signaling and regulation. As their importance is increasingly recognized, the detailed analyses of specific IDP interactions opened up new opportunities for therapeutic targeting. Yet, large scale information about IDP-mediated interactions in structural and functional details are lacking, hindering the understanding of the mechanisms underlying this distinct binding mode.

MFIB: a repository of protein complexes with mutual folding induced by binding.

Motivation: It is commonplace that intrinsically disordered proteins (IDPs) are involved in crucial interactions in the living cell. However, the study of protein complexes formed exclusively by IDPs is hindered by the lack of data and such analyses remain sporadic. Systematic studies benefited other types of protein-protein interactions paving a way from basic science to therapeutics; yet these efforts require reliable datasets that are currently lacking for synergistically folding complexes of IDPs.

Identification of potential glutaminyl cyclase inhibitors from lead-like libraries by in silico and in vitro fragment-based screening.

A glutaminyl cyclase (QC) fragment library was in silico selected by disconnection of the structure of known QC inhibitors and by lead-like 2D virtual screening of the same set. The resulting fragment library (204 compounds) was acquired from commercial suppliers and pre-screened by differential scanning fluorimetry followed by functional in vitro assays. In this way, 10 fragment hits were identified ([Formula: see text]5 % hit rate, best inhibitory activity: 16 [Formula: see text]).

The role of stabilization centers in protein thermal stability.

The definition of stabilization centers was introduced almost two decades ago. They are centers of noncovalent long range interaction clusters, believed to have a role in maintaining the three-dimensional structure of proteins by preventing their decay due to their cooperative long range interactions. Here, this hypothesis is investigated from the viewpoint of thermal stability for the first time, using a large protein thermodynamics database.

Combination of Pharmacophore Matching, 2D Similarity Search, and In Vitro Biological Assays in the Selection of Potential 5-HT6 Antagonists from Large Commercial Repositories.

Rapid in silico selection of target-focused libraries from commercial repositories is an attractive and cost-effective approach. If structures of active compounds are available, rapid 2D similarity search can be performed on multimillion compound databases, but the generated library requires further focusing. We report here a combination of the 2D approach with pharmacophore matching which was used for selecting 5-HT6 antagonists.

Prediction and analysis of intrinsically disordered proteins.

Intrinsically disordered proteins and protein regions (IDPs/IDRs) do not adopt a well-defined folded structure under physiological conditions. Instead, these proteins exist as heterogeneous and dynamical conformational ensembles. IDPs are widespread in eukaryotic proteomes and are involved in fundamental biological processes, mostly related to regulation and signaling.

A word of caution about biological inference - Revisiting cysteine covalent state predictions.

The success of methods for predicting the redox state of cysteine residues from the sequence environment seemed to validate the basic assumption that this state is mainly determined locally. However, the accuracy of predictions on randomized sequences or of non-cysteine residues remained high, suggesting that these predictions rather capture global features of proteins such as subcellular localization, which depends on composition. This illustrates that even high prediction accuracy is insufficient to validate implicit assumptions about a biological phenomenon.

Combination of 2D/3D ligand-based similarity search in rapid virtual screening from multimillion compound repositories. Selection and biological evaluation of potential PDE4 and PDE5 inhibitors.

Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost effective approach. If structures of active compounds are available rapid 2D similarity search can be performed on multimillion compound databases but the generated library requires further focusing by various 2D/3D chemoinformatics tools. We report here a combination of the 2D approach with a ligand-based 3D method (Screen3D) which applies flexible matching to align reference and target compounds in a dynamic manner and thus to assess their structural and conformational similarity.

Series of concentration-induced phase transitions in cholesterol/phosphatidylcholine mixtures.

In lipid membranes, temperature-induced transition from gel-to-fluid phase increases the lateral diffusion of the lipid molecules by three orders of magnitude. In cell membranes, a similar phase change may trigger the communication between the membrane components. Here concentration-induced phase transition properties of our recently developed statistical mechanical model of cholesterol/phospholipid mixtures are investigated.

PDBTM: Protein Data Bank of transmembrane proteins after 8 years.

The PDBTM database (available at http://pdbtm.enzim.hu), the first comprehensive and up-to-date transmembrane protein selection of the Protein Data Bank, was launched in 2004.

Disordered binding regions and linear motifs--bridging the gap between two models of molecular recognition.

Intrinsically disordered proteins (IDPs) exist without the presence of a stable tertiary structure in isolation. These proteins are often involved in molecular recognition processes via their disordered binding regions that can recognize partner molecules by undergoing a coupled folding and binding process. The specific properties of disordered binding regions give way to specific, yet transient interactions that enable IDPs to play central roles in signaling pathways and act as hubs of protein interaction networks.

CMWeb: an interactive on-line tool for analysing residue-residue contacts and contact prediction methods.

A contact map is a 2D derivative of the 3D structure of proteins, containing various residue-residue (RR) contacts within the structure. Contact maps can be used for the reconstruction of structure with high accuracy and can be predicted from the amino acid sequence. Therefore understanding the various properties of contact maps is an important step in protein structure prediction.