Many sequence variants have been linked to complex human traits and diseases, but deciphering their biological functions remains challenging, as most of them reside in noncoding DNA. Here we have systematically assessed the binding of 270 human trans...
Journal of chemical information and modeling
Jan 26, 2021
Similarity-based virtual screening is a fundamental tool in the early drug discovery process and relies heavily on molecular fingerprints. We propose a novel strategy of generating domain-specific fingerprints by training neural networks on target-sp...
Journal of chemical information and modeling
Jan 25, 2021
In the world plagued by the emergence of new diseases, it is essential that we accelerate the drug design process to develop new therapeutics against them. In recent years, deep learning-based methods have shown some success in ligand-based drug desi...
Journal of chemical information and modeling
Jan 6, 2021
The α2a adrenoceptor is a medically relevant subtype of the G protein-coupled receptor family. Unfortunately, high-throughput techniques aimed at producing novel drug leads for this receptor have been largely unsuccessful because of the complex pharm...
Predicting the structure of multi-protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage predefined structural features to di...
Journal of integrative bioinformatics
Dec 29, 2020
G protein-coupled receptors (GPCRs) play an essential role in critical human activities, and they are considered targets for a wide range of drugs. Accordingly, based on these crucial roles, GPCRs are mainly considered and focused on pharmaceutical r...
Allosteric molecules provide a powerful means to modulate protein function. However, the effect of such ligands on distal orthosteric sites cannot be easily described by classical docking methods. Here, we applied machine learning (ML) approaches to ...
Archives of biochemistry and biophysics
Dec 19, 2020
Although the use of computational methods within the pharmaceutical industry is well established, there is an urgent need for new approaches that can improve and optimize the pipeline of drug discovery and development. In spite of the fact that there...
Identification of high affinity drug-target interactions is a major research question in drug discovery. Proteins are generally represented by their structures or sequences. However, structures are available only for a small subset of biomolecules an...
To greatly expand the druggable genome, fast and accurate predictions of cryptic sites for small molecules binding in target proteins are in high demand. In this study, we have developed a fast and simple conformational sampling scheme guided by norm...