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1. Coupling dynamics and evolutionary information with structure to identify protein regulatory and functional binding sites

   https://doi.org/10.1002/prot.25749  

   Mishra, Sambit K.; Kandoi, Gaurav; Jernigan, Robert L. (June 2019, Proteins: Structure, Function, and Bioinformatics)

   Abstract Binding sites in proteins can be either specifically functional binding sites (active sites) that bind specific substrates with high affinity or regulatory binding sites (allosteric sites), that modulate the activity of functional binding sites through effector molecules. Owing to their significance in determining protein function, the identification of protein functional and regulatory binding sites is widely acknowledged as an important biological problem. In this work, we present a novel binding site prediction method, Active and Regulatory site Prediction (AR‐Pred), which supplements protein geometry, evolutionary, and physicochemical features with information about protein dynamics to predict putative active and allosteric site residues. As the intrinsic dynamics of globular proteins plays an essential role in controlling binding events, we find it to be an important feature for the identification of protein binding sites. We train and validate our predictive models on multiple balanced training and validation sets with random forest machine learning and obtain an ensemble of discrete models for each prediction type. Our models for active site prediction yield a median area under the curve (AUC) of 91% and Matthews correlation coefficient (MCC) of 0.68, whereas the less well‐defined allosteric sites are predicted at a lower level with a median AUC of 80% and MCC of 0.48. When tested on an independent set of proteins, our models for active site prediction show comparable performance to two existing methods and gains compared to two others, while the allosteric site models show gains when tested against three existing prediction methods. AR‐Pred is available as a free downloadable package athttps://github.com/sambitmishra0628/AR-PRED_source. 

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2. Factors that affect migratory Western Atlantic red knots (Calidris canutus rufa) and their prey during spring staging on Virginia’s barrier islands

   https://doi.org/10.1371/journal.pone.0270224  

   Heller, Erin L.; Karpanty, Sarah M.; Cohen, Jonathan B.; Catlin, Daniel H.; Ritter, Shannon J.; Truitt, Barry R.; Fraser, James D. (July 2022, PLOS ONE)

   Paiva, Vitor Hugo (Ed.)

   Understanding factors that influence a species’ distribution and abundance across the annual cycle is required for range-wide conservation. Thousands of imperiled red knots ( Calidris cantus rufa ) stop on Virginia’s barrier islands each year to replenish fat during spring migration. We investigated the variation in red knot presence and flock size, the effects of prey on this variation, and factors influencing prey abundance on Virginia’s barrier islands. We counted red knots and collected potential prey samples at randomly selected sites from 2007–2018 during a two-week period during early and peak migration. Core samples contained crustaceans (Orders Amphipoda and Calanoida), blue mussels ( Mytilus edulis) , coquina clams ( Donax variabilis ), and miscellaneous prey (horseshoe crab eggs ( Limulus polyphemus ), angel wing clams ( Cyrtopleura costata ), and other organisms (e.g., insect larvae, snails, worms)). Estimated red knot peak counts in Virginia during 21–27 May were highest in 2012 (11,959) and lowest in 2014 (2,857; 12-year peak migration x ¯ = 7,175, SD = 2,869). Red knot and prey numbers varied across sampling periods and substrates (i.e., peat and sand). Red knots generally used sites with more prey. Miscellaneous prey ( x ¯ = 2401.00/m 2 , SE = 169.16) influenced red knot presence at a site early in migration, when we only sampled on peat banks. Coquina clams ( x ¯ = 1383.54/m 2 , SE = 125.32) and blue mussels ( x ¯ = 777.91/m 2 , SE = 259.31) affected red knot presence at a site during peak migration, when we sampled both substrates. Few relationships between prey and red knot flock size existed, suggesting that other unmeasured factors determined red knot numbers at occupied sites. Tide and mean daily water temperature affected prey abundance. Maximizing the diversity, availability, and abundance of prey for red knots on barrier islands requires management that encourages the presence of both sand and peat bank intertidal habitats. 

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3. Assembly of Synaptic Protein–DNA Complexes: Critical Role of Non-Specific Interactions

   https://doi.org/10.3390/ijms24129800  

   Vemulapalli, Sridhar; Hashemi, Mohtadin; Kolomeisky, Anatoly B.; Lyubchenko, Yuri L. (June 2023, International Journal of Molecular Sciences)

   The synaptic protein–DNA complexes, formed by specialized proteins that bridge two or more distant sites on DNA, are critically involved in various genetic processes. However, the molecular mechanism by which the protein searches for these sites and how it brings them together is not well understood. Our previous studies directly visualized search pathways used by SfiI, and we identified two pathways, DNA threading and site-bound transfer pathways, specific to the site-search process for synaptic DNA–protein systems. To investigate the molecular mechanism behind these site-search pathways, we assembled complexes of SfiI with various DNA substrates corresponding to different transient states and measured their stability using a single-molecule fluorescence approach. These assemblies corresponded to specific–specific (synaptic), non-specific–non-specific (non-specific), and specific–non-specific (pre-synaptic) SfiI–DNA states. Unexpectedly, an elevated stability in pre-synaptic complexes assembled with specific and non-specific DNA substrates was found. To explain these surprising observations, a theoretical approach that describes the assembly of these complexes and compares the predictions with the experiment was developed. The theory explains this effect by utilizing entropic arguments, according to which, after the partial dissociation, the non-specific DNA template has multiple possibilities of rebinding, effectively increasing the stability. Such difference in the stabilities of SfiI complexes with specific and non-specific DNA explains the utilization of threading and site-bound transfer pathways in the search process of synaptic protein–DNA complexes discovered in the time-lapse AFM experiments. 

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4. Khovanov Laplacian and Khovanov Dirac for knots and links

   https://doi.org/10.1088/2632-072X/adde9f  

   Jones, Benjamin; Wei, Guo-Wei (June 2025, Journal of Physics: Complexity)

   Abstract Khovanov homology has been the subject of much study in knot theory and low dimensional topology since 2000. This work introduces a Khovanov Laplacian and a Khovanov Dirac to study knot and link diagrams. The harmonic spectrum of the Khovanov Laplacian or the Khovanov Dirac retains the topological invariants of Khovanov homology, while their non-harmonic spectra reveal additional information that is distinct from Khovanov homology. 

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5. A bipartite thermodynamic-kinetic contribution by an activating mutation to RDF-independent excision by a phage serine integrase

   https://doi.org/10.1093/nar/gkaa401  

   Fan, Hsiu-Fang; Su, Bo-Yu; Ma, Chien-Hui; Rowley, Paul A; Jayaram, Makkuni (June 2020, Nucleic Acids Research)

   null (Ed.)

   Abstract Streptomyces phage ϕC31 integrase (Int)—a large serine site-specific recombinase—is autonomous for phage integration (attP x attB recombination) but is dependent on the phage coded gp3, a recombination directionality factor (RDF), for prophage excision (attL x attR recombination). A previously described activating mutation, E449K, induces Int to perform attL x attR recombination in the absence of gp3, albeit with lower efficiency. E449K has no adverse effect on the competence of Int for attP x attB recombination. Int(E449K) resembles Int in gp3 mediated stimulation of attL x attR recombination and inhibition of attP x attB recombination. Using single-molecule analyses, we examined the mechanism by which E449K activates Int for gp3-independent attL x attR recombination. The contribution of E449K is both thermodynamic and kinetic. First, the mutation modulates the relative abundance of Int bound attL-attR site complexes, favoring pre-synaptic (PS) complexes over non-productively bound complexes. Roughly half of the synaptic complexes formed from Int(E449K) pre-synaptic complexes are recombination competent. By contrast, Int yields only inactive synapses. Second, E449K accelerates the dissociation of non-productively bound complexes and inactive synaptic complexes formed by Int. The extra opportunities afforded to Int(E499K) in reattempting synapse formation enhances the probability of success at fruitful synapsis. 

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