Protein-ligand binding affinity prediction exploiting sequence constituent homology.

Motivation: Molecular docking is a commonly used approach for estimating binding conformations and their resultant binding affinities. Machine learning has been successfully deployed to enhance such affinity estimations. Many methods of varying complexity have been developed making use of some or all the spatial and categorical information available in these structures.

Recent molecularly imprinted polymers applications in bioanalysis.

Molecular imprinted polymers (MIPs) as extraordinary compounds with unique features have presented a wide range of applications and benefits to researchers. In particular when used as a sorbent in sample preparation methods for the analysis of biological samples and complex matrices. Its application in the extraction of medicinal species has attracted much attention and a growing interest.

Batched Bayesian Optimization for Drug Design in Noisy Environments.

The early stages of the drug design process involve identifying compounds with suitable bioactivities via noisy assays. As databases of possible drugs are often very large, assays can only be performed on a subset of the candidates. Selecting which assays to perform is best done within an active learning process, such as batched Bayesian optimization, and aims to reduce the number of assays that must be performed.

A simple spatial extension to the extended connectivity interaction features for binding affinity prediction.

The representation of the protein-ligand complexes used in building machine learning models play an important role in the accuracy of binding affinity prediction. The Extended Connectivity Interaction Features (ECIF) is one such representation. We report that (i) including the discretized distances between protein-ligand atom pairs in the ECIF scheme improves predictive accuracy, and (ii) in an evaluation using gradient boosted trees, we found that the resampling method used in selecting the best hyperparameters has a strong effect on predictive performance, especially for benchmarking purposes.

Functionalized graphene oxide tablets for sample preparation of drugs in biological fluids: Extraction of ritonavir, a HIV protease inhibitor, from human saliva and plasma using LC-MS/MS.

In this work, graphene oxide-based tablets (GO-Tabs) were prepared by applying a thin layer of functionalized GO on a polyethylene substrate. The GO was functionalized with amine groups (-NH ) by poly(ethylene glycol)bis(3-aminopropyl) terminated (GO-NH -PEG-NH ). The functionalized GO-Tabs were used for the extraction of ritonavir (RTV) in human saliva samples.

Recent applications of microextraction sample preparation techniques in biological samples analysis.

Analysis of biological samples is affected by interfering substances with chemical properties similar to those of the target analytes, such as drugs. Biological samples such as whole blood, plasma, serum, urine and saliva must be properly processed for separation, purification, enrichment and chemical modification to meet the requirements of the analytical instruments. This causes the sample preparation stage to be of undeniable importance in the analysis of such samples through methods such as microextraction techniques.

Microextraction approaches for bioanalytical applications: An overview.

Biological samples are usually complex matrices due to the presence of proteins, salts and a variety of organic compounds with chemical properties similar to those of the target analytes. Therefore, sample preparation is often mandatory in order to isolate the analytes from troublesome matrices before instrumental analysis. Because the number of samples in drug development, doping analysis, forensic science, toxicological analysis, and preclinical and clinical assays is steadily increasing, novel high throughput sample preparation approaches are calling for.

Distinct Requirements for Tail-Anchored Membrane Protein Biogenesis in Escherichia coli.

Tail-anchored membrane proteins (TAMPs) are a distinct subset of inner membrane proteins (IMPs) characterized by a single C-terminal transmembrane domain (TMD) that is responsible for both targeting and anchoring. Little is known about the routing of TAMPs in bacteria. Here, we have investigated the role of TMD hydrophobicity in tail-anchor function in and its influence on the choice of targeting/insertion pathway.

Recent Applications of Molecularly Imprinted Sol-Gel Methodology in Sample Preparation.

Due to their selectivity and chemical stability, molecularly imprinted polymers have attracted great interest in sample preparation. Imprinted polymers have been applied for the extraction and the enrichment of different sorts of trace analytes in biological and environmental samples before their analysis. Additionally, MIPs are utilized in various sample preparation techniques such as SPE, SPME, SBSE and MEPS.

On-line determination of sarcosine in biological fluids utilizing dummy molecularly imprinted polymers in microextraction by packed sorbent.

Several years ago, sarcosine received attention as a prostate-cancer marker. Prostate cancer is one of the most widespread types of tumor diseases in men. The prostate-specific antigen is normally used as a marker, and it can only be detected in blood with a sensitivity of approximately 80%.

Preparation of monolithic molecularly imprinted polymer sol-gel packed tips for high-throughput bioanalysis: extraction and quantification of L-tyrosine in human plasma and urine samples utilizing liquid chromatography and tandem mass spectrometry.

In situ monolithic molecularly imprinted polymer sol-gel packed tips (MMSTs) were prepared and evaluated for the extraction of lung cancer biomarker L-tyrosine (Tyr) from human plasma and urine samples. Several extraction parameters such as the conditioning, washing and elution solutions, pH and time were investigated. The enrichment factor (EF) and extraction recovery (ER) were studied.

Dried saliva spot as a sampling technique for saliva samples.

For the first time, dried saliva spot (DSS) was used as a sampling technique for saliva samples. In the DSS technique 50 μL of saliva was collected on filter paper and the saliva was then extracted with an organic solvent. The local anesthetic lidocaine was used as a model compound, which was determined in the DSS using liquid chromatography and mass spectrometry.

PconsC: combination of direct information methods and alignments improves contact prediction.

Summary: Recently, several new contact prediction methods have been published. They use (i) large sets of multiple aligned sequences and (ii) assume that correlations between columns in these alignments can be the results of indirect interaction. These methods are clearly superior to earlier methods when it comes to predicting contacts in proteins.

Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected.

Evaluation of microextraction by packed sorbent and micro-liquid chromatography-tandem mass spectrometry as a green approach in bioanalysis.

In this study the use of micro-liquid chromatography coupled to tandem mass spectrometry (μLC-MS/MS) was investigated in routine bioanalysis application for separation and quantification of pro-drug AZD6319 (developed for aldezheimer treatment). Microextraction by packed sorbent (MEPS) was used as sample clean-up method. The focus of this study was put on the evaluation of the usability of smaller column diameters such as 1.