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Understanding the biological functions of proteins is of fundamental importance in modern biology. To represent a function of proteins, Gene Ontology (GO), a controlled vocabulary, is frequently used, because it is easy to handle by computer programs avoiding open-ended text interpretation. Particularly, the majority of current protein function prediction methods rely on GO terms. However, the extensive list of GO terms that describe a protein function can pose challenges for biologists when it comes to interpretation. In response to this issue, we developed GO2Sum (Gene Ontology terms Summarizer), a model that takes a set of GO terms as input and generates a human-readable summary using the T5 large language model. GO2Sum was developed by fine-tuning T5 on GO term assignments and free-text function descriptions for UniProt entries, enabling it to recreate function descriptions by concatenating GO term descriptions. Our results demonstrated that GO2Sum significantly outperforms the original T5 model that was trained on the entire web corpus in generating Function, Subunit Structure, and Pathway paragraphs for UniProt entries.

 

Domains are functional and structural units of proteins that govern various biological functions performed by the proteins. Therefore, the characterization of domains in a protein can serve as a proper functional representation of proteins. Here, we employ a self-supervised protocol to derive functionally consistent representations for domains by learning domain-Gene Ontology (GO) co-occurrences and associations. The domain embeddings we constructed turned out to be effective in performing actual function prediction tasks. Extensive evaluations showed that protein representations using the domain embeddings are superior to those of large-scale protein language models in GO prediction tasks. Moreover, the new function prediction method built on the domain embeddings, named Domain-PFP, substantially outperformed the state-of-the-art function predictors. Additionally, Domain-PFP demonstrated competitive performance in the CAFA3 evaluation, achieving overall the best performance among the top teams that participated in the assessment.

 

The tertiary structures of an increasing number of biological macromolecules have been determined using cryo-electron microscopy (cryo-EM). However, there are still many cases where the resolution is not high enough to model the molecular structures with standard computational tools. If the resolution obtained is near the empirical borderline (3–4.5 Å), improvement in the map quality facilitates structure modeling.

We report EM-GAN, a novel approach that modifies an input cryo-EM map to assist protein structure modeling. The method uses a 3D generative adversarial network (GAN) that has been trained on high- and low-resolution density maps to learn the density patterns, and modifies the input map to enhance its suitability for modeling. The method was tested extensively on a dataset of 65 EM maps in the resolution range of 3–6 Å and showed substantial improvements in structure modeling using popular protein structure modeling tools.

https://github.com/kiharalab/EM-GAN, Google Colab: https://tinyurl.com/3ccxpttx.

 

Protein–DNA interactions play an important role in various biological processes such as gene expression, replication, and transcription. Understanding the important features that dictate the binding affinity of protein-DNA complexes and predicting their affinities is important for elucidating their recognition mechanisms. In this work, we have collected the experimental binding free energy (ΔG) for a set of 391 Protein-DNA complexes and derived several structure-based features such as interaction energy, contact potentials, volume and surface area of binding site residues, base step parameters of the DNA and contacts between different types of atoms. Our analysis on relationship between binding affinity and structural features revealed that the important factors mainly depend on the number of DNA strands as well as functional and structural classes of proteins. Specifically, binding site properties such as number of atom contacts between the DNA and protein, volume of protein binding sites and interaction-based features such as interaction energies and contact potentials are important to understand the binding affinity. Further, we developed multiple regression equations for predicting the binding affinity of protein-DNA complexes belonging to different structural and functional classes. Our method showed an average correlation and mean absolute error of 0.78 and 0.98 kcal/mol, respectively, between the experimental and predicted binding affinities on a jack-knife test. We have developed a webserver, PDA-PreD (Protein-DNA Binding affinity predictor), for predicting the affinity of protein-DNA complexes and it is freely available at https://web.iitm.ac.in/bioinfo2/pdapred/ 

Structural bioinformatics analyzes protein structural models with the goal of uncovering molecular drivers of food functionality. This field aims to develop tools that can rapidly extract relevant information from protein databases as well as organize this information for researchers interested in studying protein functionality. Food bioinformaticians take advantage of millions of protein amino acid sequences and structures contained within these databases, extracting features such as surface hydrophobicity that are then used to model functionality, including solubility, thermostability, and emulsification. This work is aided by a protein structure–function relationship framework, in which bioinformatic properties are linked to physicochemical experimentation. Strong bioinformatic correlations exist for protein secondary structure, electrostatic potential, and surface hydrophobicity. Modeling changes in protein structures through molecular mechanics is an increasingly accessible field that will continue to propel food science research. 

Driving mechanisms of many biological functions in a cell include physical interactions of proteins. As protein-protein interactions (PPIs) are also important in disease development, protein-protein interactions are highlighted in the pharmaceutical industry as possible therapeutic targets in recent years. To understand the variety of protein-protein interactions in a proteome, it is essential to establish a method that can identify similarity and dissimilarity between protein-protein interactions for inferring the binding of similar molecules, including drugs and other proteins. In this study, we developed a novel method, protein-protein interaction-Surfer, which compares and quantifies similarity of local surface regions of protein-protein interactions. protein-protein interaction-Surfer represents a protein-protein interaction surface with overlapping surface patches, each of which is described with a three-dimensional Zernike descriptor (3DZD), a compact mathematical representation of 3D function. 3DZD captures both the 3D shape and physicochemical properties of the protein surface. The performance of protein-protein interaction-Surfer was benchmarked on datasets of protein-protein interactions, where we were able to show that protein-protein interaction-Surfer finds similar potential drug binding regions that do not share sequence and structure similarity. protein-protein interaction-Surfer is available at https://kiharalab.org/ppi-surfer . 

Suncus etruscusis one of the world’s smallest mammals, with an average body mass of about 2 grams. The Etruscan shrew’s small body is accompanied by a very high energy demand and numerous metabolic adaptations. Here we report a chromosome-level genome assembly using PacBio long read sequencing, 10X Genomics linked short reads, optical mapping, and Hi-C linked reads. The assembly is partially phased, with the 2.472 Gbp primary pseudohaplotype and 1.515 Gbp alternate. We manually curated the primary assembly and identified 22 chromosomes, including X and Y sex chromosomes. The NCBI genome annotation pipeline identified 39,091 genes, 19,819 of them protein-coding. We also identified segmental duplications, inferred GO term annotations, and computed orthologs of human and mouse genes. This reference-quality genome will be an important resource for research on mammalian development, metabolism, and body size control.