A unified statistical model to support local sequence order independent similarity searching for ligand-binding sites and its application to genome-based drug discovery is a research paper published in Bioinformatics (2009). On theSindex it has a DataRank of 3.4. It has been cited 96 times, with 71 citing works in its 1-hop citation network. Its calibrated FAIR score is 68/100.
Functional relationships between proteins that do not share global structure similarity can be established by detecting their ligand-binding-site similarity. For a large-scale comparison, it is critical to accurately and efficiently assess the statistical significance of this similarity. Here, we report an efficient statistical model that supports local sequence order independent ligand-binding-site similarity searching. Most existing statistical models only take into account the matching vertices between two sites that are defined by a fixed number of points. In reality, the boundary of the binding site is not known or is dependent on the bound ligand making these approaches limited. To address these shortcomings and to perform binding-site mapping on a genome-wide scale, we developed a sequence-order independent profile-profile alignment (SOIPPA) algorithm that is able to detect local similarity between unknown binding sites a priori. The SOIPPA scoring integrates geometric, evolutionary and physical information into a unified framework. However, this imposes a significant challenge in assessing the statistical significance of the similarity because the conventional probability model that is based on fixed-point matching cannot be applied. Here we find that scores for binding-site matching by SOIPPA follow an extreme value distribution (EVD). Benchmark studies show that the EVD model performs at least two-orders faster and is more accurate than the non-parametric statistical method in the previous SOIPPA version. Efficient statistical analysis makes it possible to apply SOIPPA to genome-based drug discovery. Consequently, we have applied the approach to the structural genome of Mycobacterium tuberculosis to construct a protein-ligand interaction network. The network reveals highly connected proteins, which represent suitable targets for promiscuous drugs.
FAIR checklist signals are shown for context only and do not affect DataRank scoring.
Calibrated FAIR score — a parallel quality metric, independent of the DataRank citation score. See the full evaluation →
Base Score Contribution
0.686
From this paper's citation signal
Citation Network Contribution
2.7
From 63 citing papers with measurable signal
Ranked by citation count — the same ordering the engine uses when summing log1p(Cq) over citers.
DataRank blends this paper's own citation count with the influence of the papers that cite it. Here, roughly 20% comes from its base citations and 80% from the citation network (63 citing papers contributed measurable signal).
Citers are pulled from OpenAlex sorted by cited_by_count:descand capped per paper, so when the cap binds we keep the highest-signal references and the score is reproducible across reruns.
Click a node to highlight its connections. Use scroll to zoom. Drag to pan.