DOI: 10.6084/m9.figshare.28770794
title: Integrated Computational Study of ORF10 Binding Sites: DNA, FMN, and RNA Interaction Predictions

description: This dataset provides comprehensive predictions of ligand-binding sites for the ORF10 protein, generated through computational modeling and clustering techniques. As an independent researcher, I aimed to identify key residues involved in interactions with DNA, RNA, FMN, and other small molecules, providing insights into ORF10's potential functional roles. The analysis includes raw predictions, clustered binding site residues, predicted complex structures, and template ligand summaries. Below is a detailed breakdown of the included datasets:<br>1. Raw Binding Site Residue Predictions (predicted_bsr.txt)This file contains the raw output of predicted binding site residues for ORF10, generated using computational tools.Key findings include:SITE 1 : A DNA-binding site at residues 2, 4, 5, 10, 11, 12, 13, 15 , with moderate confidence (C-Score: 0.24).SITE 2 : A multi-functional site interacting with DNA, RNA, and small molecules at residues 10, 11, 12, 14, 19 , with lower confidence (C-Score: 0.15).SITE 3 : A high-confidence FMN-binding site at residues 18, 20 (C-Score: 0.08).SITE 4 : A speculative RNA-binding site at residues 3, 8 (C-Score: 0.04).These predictions provide residue-level details and associated ligands, forming the basis for further analysis and experimental validation.2. Clustered Predictions (clustering.txt)This file groups similar binding site predictions into clusters based on spatial proximity and residue overlap, highlighting consensus binding sites across multiple templates.Key clusters include:Cluster 1 : A conserved DNA-binding site at residues 2, 4, 5, 10, 11, 12, 13, 15 , supported by multiple templates (Confidence Range: 0.04–0.13).Cluster 2 : A multi-functional site interacting with DNA and small molecules at residues 10, 11, 12, 14, 19 , with moderate confidence (Confidence Range: 0.06–0.52).Cluster 3 : A high-confidence FMN-binding site at residues 18, 20 (Confidence Range: 0.44–0.53).Cluster 4 : A speculative RNA-binding site at residues 3, 8 (Confidence: 0.04).Clustering enhances the reliability of predictions by identifying consistent patterns across templates.3. Predicted Complex StructureThis dataset provides detailed information about the predicted complex structure of ORF10 with its ligands, focusing on the top-ranked binding site.Key details include:Rank 1 : A DNA-binding site at residues G2, I4, N5, P10, F11, T12, I13, S15 , with moderate confidence (C-Score: 0.24) and docking energy (-1), indicating weak but favorable binding.Rank 2 : An additional DNA-binding site at residues P10, F11, T12, Y14, C19 , with overlapping residues and lower confidence (C-Score: 0.15).Rank 3 : An FMN-binding site at residues L18, R20 , with moderate structural similarity (TM-Score: 0.40) but limited template support.Rank 4 : A speculative RNA-binding site at residues Y3, A8 , with very low confidence (C-Score: 0.04).The predicted complex structure highlights specific residues and their roles in ligand interactions, offering a foundation for experimental validation.4. Summary of Template LigandsThis summary provides an overview of ligands predicted to interact with ORF10, based on the frequency of ligand templates used in the analysis.Key findings include:DNA : The most frequently observed ligand (6 templates: 6dfcA, 5vmvA, 5vmzA, 5vmyA, 5vmwA, 6df9A), strongly supporting ORF10's interaction with DNA.FMN : Observed in 1 template (2i51A), suggesting a potential role in cofactor binding.RNA : Observed in 1 template (6gawBT), but with low confidence, making this prediction speculative.The summary reinforces the prominence of DNA as the primary ligand and highlights secondary interactions with FMN.Significance of the FindingsDNA-Binding Site : Residues P10, F11, T12 are consistently predicted across multiple datasets, reinforcing their role in DNA binding. These residues may be critical for ORF10's interaction with host or viral DNA.FMN-Binding Site : Residues L18, R20 are predicted to bind FMN, suggesting a potential role in redox reactions or cofactor-mediated processes.RNA-Binding Site : Residues Y3, A8 are weakly predicted to bind RNA, requiring further validation before drawing conclusions.Multi-Functional Site : Residues 10, 11, 12, 14, 19 may interact with both DNA and small molecules, indicating dual functionality.LimitationsSome predictions have low confidence scores and require experimental validation.Results are based on computational modeling and depend on available structural templates, which may not fully represent ORF10's actual structure.Weak docking energies (e.g., -1 for DNA) suggest transient or low-affinity interactions, possibly requiring additional factors for stable binding.Potential ApplicationsExperimental Validation : Use mutagenesis, EMSA, or X-ray crystallography to confirm predicted binding sites.Drug Design : Target key residues (e.g., P10, F11, T12) for designing inhibitors or modulators of ORF10's activity.Functional Studies : Investigate ORF10's roles in DNA-related processes, cofactor interactions, or RNA regulation.Files Includedpredicted_bsr.txt: Raw output of predicted binding site residues.clustering.txt: Clustered predictions grouping similar binding sites.complex_structure_summary.txt: Detailed predictions of ORF10-ligand complex structures.template_ligands_summary.txt: Summary of ligands and their frequencies across templates.summary of predicted bsr in text fileinput_orf10.pdb: Original protein structure used for analysis.visualizations/: Images or interactive visualizations of predicted binding sites.AcknowledgmentsWhile computational tools were used for initial predictions, the findings focus on consensus binding sites and are not tool-specific. The work reflects an independent effort to analyze ORF10's functional roles and provide a resource for the scientific community.