An interactive visualization tool for educational outreach in protein contact map overlap analysis.

Recent advancements in contact map-based protein three-dimensional (3D) structure prediction have been driven by the evolution of deep learning algorithms. However, the gap in accessible software tools for novices in this domain remains a significant challenge. This study introduces GoFold, a novel, standalone graphical user interface (GUI) designed for beginners to perform contact map overlap (CMO) problems for better template selection.

Contact-Assisted Threading in Low-Homology Protein Modeling.

The ability to successfully predict the three-dimensional structure of a protein from its amino acid sequence has made considerable progress in the recent past. The progress is propelled by the improved accuracy of deep learning-based inter-residue contact map predictors coupled with the rising growth of protein sequence databases. Contact map encodes interatomic interaction information that can be exploited for highly accurate prediction of protein structures via contact map threading even for the query proteins that are not amenable to direct homology modeling.

rrQNet: Protein contact map quality estimation by deep evolutionary reconciliation.

Protein contact maps have proven to be a valuable tool in the deep learning revolution of protein structure prediction, ushering in the recent breakthrough by AlphaFold2. However, self-assessment of the quality of predicted structures are typically performed at the granularity of three-dimensional coordinates as opposed to directly exploiting the rotation- and translation-invariant two-dimensional (2D) contact maps. Here, we present rrQNet, a deep learning method for self-assessment in 2D by contact map quality estimation.

DisCovER: distance- and orientation-based covariational threading for weakly homologous proteins.

Threading a query protein sequence onto a library of weakly homologous structural templates remains challenging, even when sequence-based predicted contact or distance information is used. Contact-assisted or distance-assisted threading methods utilize only the spatial proximity of the interacting residue pairs for template selection and alignment, ignoring their orientation. Moreover, existing threading methods fail to consider the neighborhood effect induced by the query-template alignment.

Recent Advances in Protein Homology Detection Propelled by Inter-Residue Interaction Map Threading.

Sequence-based protein homology detection has emerged as one of the most sensitive and accurate approaches to protein structure prediction. Despite the success, homology detection remains very challenging for weakly homologous proteins with divergent evolutionary profile. Very recently, deep neural network architectures have shown promising progress in mining the coevolutionary signal encoded in multiple sequence alignments, leading to reasonably accurate estimation of inter-residue interaction maps, which serve as a rich source of additional information for improved homology detection.

Hybridized distance- and contact-based hierarchical structure modeling for folding soluble and membrane proteins.

Crystallography and NMR system (CNS) is currently a widely used method for fragment-free ab initio protein folding from inter-residue distance or contact maps. Despite its widespread use in protein structure prediction, CNS is a decade-old macromolecular structure determination system that was originally developed for solving macromolecular geometry from experimental restraints as opposed to predictive modeling driven by interaction map data. As such, the adaptation of the CNS experimental structure determination protocol for ab initio protein folding is intrinsically anomalous that may undermine the folding accuracy of computational protein structure prediction.

PolyFold: An interactive visual simulator for distance-based protein folding.

Recent advances in distance-based protein folding have led to a paradigm shift in protein structure prediction. Through sufficiently precise estimation of the inter-residue distance matrix for a protein sequence, it is now feasible to predict the correct folds for new proteins much more accurately than ever before. Despite the exciting progress, a dedicated visualization system that can dynamically capture the distance-based folding process is still lacking.

QDeep: distance-based protein model quality estimation by residue-level ensemble error classifications using stacked deep residual neural networks.

Motivation: Protein model quality estimation, in many ways, informs protein structure prediction. Despite their tight coupling, existing model quality estimation methods do not leverage inter-residue distance information or the latest technological breakthrough in deep learning that has recently revolutionized protein structure prediction.

Results: We present a new distance-based single-model quality estimation method called QDeep by harnessing the power of stacked deep residual neural networks (ResNets).

Evaluating the significance of contact maps in low-homology protein modeling using contact-assisted threading.

The development of improved threading algorithms for remote homology modeling is a critical step forward in template-based protein structure prediction. We have recently demonstrated the utility of contact information to boost protein threading by developing a new contact-assisted threading method. However, the nature and extent to which the quality of a predicted contact map impacts the performance of contact-assisted threading remains elusive.

Does inclusion of residue-residue contact information boost protein threading?

Template-based modeling is considered as one of the most successful approaches for protein structure prediction. However, reliably and accurately selecting optimal template proteins from a library of known protein structures having similar folds as the target protein and making correct alignments between the target sequence and the template structures, a template-based modeling technique known as threading, remains challenging, particularly for non- or distantly-homologous protein targets. With the recent advancement in protein residue-residue contact map prediction powered by sequence co-evolution and machine learning, here we systematically analyze the effect of inclusion of residue-residue contact information in improving the accuracy and reliability of protein threading.