Transferable neural networks for enhanced sampling of protein dynamics

Variational auto-encoder frameworks have demonstrated success in reducing complex nonlinear dynamics in molecular simulation to a single non-linear embedding. In this work, we illustrate how this non-linear latent embedding can be used as a collective variable for enhanced sampling, and present a simple modification that allows us to rapidly perform sampling in multiple related systems. We first demonstrate our method is able to describe the effects of force field changes in capped alanine dipeptide after learning a model using AMBER99. We further provide a simple extension to variational dynamics encoders that allows the model to be trained in a more efficient manner on larger systems by encoding the outputs of a linear transformation using time-structure based independent component analysis (tICA). Using this technique, we show how such a model trained for one protein, the WW domain, can efficiently be transferred to perform enhanced sampling on a related mutant protein, the GTT mutation. This method shows promise for its ability to rapidly sample related systems using a single transferable collective variable and is generally applicable to sets of related simulations, enabling us to probe the effects of variation in increasingly large systems of biophysical interest.Comment: 20 pages, 10 figure

Compositional Deep Probabilistic Models of DNA Encoded Libraries

DNA-Encoded Library (DEL) has proven to be a powerful tool that utilizes combinatorially constructed small molecules to facilitate highly-efficient screening assays. These selection experiments, involving multiple stages of washing, elution, and identification of potent binders via unique DNA barcodes, often generate complex data. This complexity can potentially mask the underlying signals, necessitating the application of computational tools such as machine learning to uncover valuable insights. We introduce a compositional deep probabilistic model of DEL data, DEL-Compose, which decomposes molecular representations into their mono-synthon, di-synthon, and tri-synthon building blocks and capitalizes on the inherent hierarchical structure of these molecules by modeling latent reactions between embedded synthons. Additionally, we investigate methods to improve the observation models for DEL count data such as integrating covariate factors to more effectively account for data noise. Across two popular public benchmark datasets (CA-IX and HRP), our model demonstrates strong performance compared to count baselines, enriches the correct pharmacophores, and offers valuable insights via its intrinsic interpretable structure, thereby providing a robust tool for the analysis of DEL data

Study On the Parasites of Falcons in the United Arab Emirates

Sakers Falco cherrug, Gyrfalcons Falco rusticolus, Peregrines Falco peregrilllls, in addition to Hybrids (saker X gyrfalcon, or gyrfalcon X peregrine), were found to be the most popular species of falcons in United Arab Emirates (UAE). The importance of falcons and falconry in Arabia was highlighted with a brief history of falconry in Arabia. The study focused on the prevalence of intestinal parasites (coccidia, helminthes and nematodes) and blood parasites (Haemoproteus sp. and Leucocytozoon sp.) as well as ecto-parasites (Ticks and Mites) of these falcons, with discussion on the possible sources of infection in view of the epizootiology of these parasites. 100 falcons, 89 females and 11 males, were studied at random. Of these 100 falcons, 50 falcons were considered as resident falcons having spent a period of 1-4 years in the UAE, the rest (50 falcons) with less than 1-year residence were considered imported falcons . The falcons were identified, thin blood smears were taken stained with Giemsa, examined for blood parasites and positive smears were identified. Fresh feces were collected for macroscopic examination to recognize adult worms, segments of tapeworms or fly larvae, then fecal materials were prepared (direct and floatation methods) for microscopic examination to detect protozoan cyst and helminthes eggs. Three techniques: feathers inspection, insecticide spray, and shaking the body in full sun light, were used for collecting ecto-parasites. The results were presented in term of numbers and percentages of non-infected and infected imported and resident falcons in relation to species and sex. 52% (26/50) of imported falcons showed parasitic infections, while 38% (19/50) of resident falcons were found to be infected. The results were compared with those of other researchers. Emphasis was also laid on the pathological aspects of parasitic infection in falcons. Recommendations that would lead to significant decrease in the infection rates in falcons in the UAE were made

Characteristics and anticancer properties of Sunitinib malate-loaded poly-lactic-co-glycolic acid nanoparticles against human colon cancer HT-29 cells lines

Purpose: To develop poly-lactic-co-glycolic acid (PLGA) -based nanoparticles (NPs) for the delivery of sunitinib malate (STM) to colon cancer cells.Methods: Three different formulations (F1 – F3) were developed by nano-precipitation technique using various concentrations of PLGA. The NPs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment, and drug loading, using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, in vitro drug release and anticancer studies were carried out on the formulations.Results: Among the three NPs, optimized NP (F3) of STM was chosen for in vitro anti-cancer study against H-29 human colon cancer cells lines based on its particle size (132.9 nm), PDI (0.115), zeta potential (-38.12 mV), entrapment efficiency (52.42 %), drug loading (5.24 %), and drug release (91.26 % in 48 h). A significant anti-cancer activity of the optimized NPs was observed, relative to free STM.Conclusion: These findings suggest that STM-loaded NPs possess significant anti-cancer activity against human colon cancer HT-29 cells lines.Keywords: Sunitinib malate, Poly-lactic-co-glycolic acid, Nanoparticles, Colon cance