With currently more than 126 000 publicly available structures and an increasing growth rate, the Protein Data Bank constitutes a rich data source for structure-driven research in fields like drug discovery, crop science biotechnology general. Typical workflows these areas involve manifold computational tools analysis prediction of molecular functions. Here, we present ProteinsPlus web server that offers unified easy-to-use interface to broad range early phase structure-based modeling. This...

Abstract Due to the increasing amount of publicly available protein structures searching, enriching and investigating these data still poses a challenging task. The ProteinsPlus web service (https://proteins.plus) offers broad range tools addressing challenges. interface tool collection focusing on protein–ligand interactions has been geared towards easy intuitive access large variety functionality for life scientists. Since our last publication, extended by additional services as well it...

We developed a cheminformatics pipeline for the fully automated selection and extraction of high-quality protein-bound ligand conformations from X-ray structural data. The evaluates validity accuracy 3D structures small molecules according to multiple criteria, including their fit electron density physicochemical properties. Using this approach, we compiled two datasets Protein Data Bank (PDB): comprehensive dataset diversified subset 4626 2912 structures, respectively. were applied...

Abstract We have demonstrated a prototypical hybrid classical and quantum computational workflow for the quantification of protein–ligand interactions. The combines density matrix embedding theory (DMET) procedure with variational eigensolver (VQE) approach finding molecular electronic ground states. A series ‐secretase (BACE1) inhibitors is rank‐ordered using binding energy differences calculated on latest superconducting transmon (IBM) trapped‐ion (Quantinuum) noisy intermediate scale...

Protein–ligand interactions are the fundamental basis for molecular design in pharmaceutical research, biocatalysis, and agrochemical development. Especially hydrogen bonds known to have special geometric requirements therefore deserve a detailed analysis. In modeling approaches more general description of bond geometries, using distance directionality, is applied. A first study their geometries was performed based on 15 protein structures 1982. Currently there about 95 000 protein–ligand...

Macromolecular structures resolved by X-ray crystallography are essential for life science research. While some methods exist to automatically quantify the quality of electron density fit, none them is without flaws. Especially question how well individual parts like atoms, small fragments, or molecules supported difficult quantify. taking experimental uncertainties correctly into account, they do not offer an answer on reliable atom position is. A rapid quantification this atomic...

Computer-aided drug design methods such as docking, pharmacophore searching, 3D database and the creation of 3D-QSAR models need conformational ensembles to handle flexibility small molecules. Here, we present Conformator, an accurate effective knowledge-based algorithm for generating conformer ensembles. With 99.9% all test molecules processed, Conformator stands out by its robustness with respect input formats, molecular geometries, handling macrocycles. extended set rules sampling torsion...

Abstract Protein folding has attracted considerable research effort in biochemistry recent decades. In this work, we explore the potential of quantum computing to solve a simplified version protein folding. More precisely, numerically investigate performance Quantum Approximate Optimization Algorithm (QAOA) sampling low-energy conformations short peptides. We start by benchmarking algorithm on an even simpler problem: self-avoiding walks. Motivated promising results, then apply more complete...

Scoring and numerical optimization of protein–ligand poses is an integral part docking tools. Although many scoring functions exist, them are not continuously differentiable they rarely explicitly analyzed with respect to their behavior. Here, we present a consistent scheme for pose gradient-based optimization. It consists novel variant the BFGS algorithm enabling step-length control, named LSL-BFGS (limited step length BFGS), empirical JAMDA function designed prediction good optimizability....

The Torsion Library contains hundreds of rules for small molecule conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by molecular design experts. torsion encoded as SMARTS patterns categorize rotatable bonds via a traffic light coloring scheme. We systematically revised all to better identify highly strained minimize number false alerts CSD X-ray structures. For this new release, we added or substantially modified 78 reviewed angles tolerance...

The Torsion Library is a collection of torsion motifs associated with angle distributions, derived from crystallographic databases. It used in strain assessment, conformer generation, and geometry optimization. A hierarchical structure expert curated SMARTS defines the chemical environments rotatable bonds associates these preferred angles. can be very complex full implications, which make them difficult to maintain manually. Recent developments automatically comparing patterns applied...

Quantum computing for the biological sciences is an area of rapidly growing interest, but specific industrial applications remain elusive. Markov chain Monte Carlo has been proposed as a method accelerating broad class computational problems, including problems pharmaceutical interest. Here we investigate prospects quantum advantage via this approach, by applying it to problem modelling antibody structure, crucial task in drug development. To minimize resources required while maintaining...

Abstract Motivation Three-dimensional protein structures are important starting points for elucidating function and applications like drug design. Computational methods in this area rely on high quality validation datasets which usually manually assembled. Due to the increase published as well increasing demand specially tailored datasets, automatic procedures should be adopted. Results StructureProfiler is a new tool automatic, objective customizable profiling of X-ray based most frequently...

ABSTRACT Reliable computational prediction of protein side chain conformations and the energetic impact amino acid mutations are key aspects for optimization biotechnologically relevant enzymatic reactions using structure‐based design. By improving stability, higher yields can be achieved. In addition, tuning substrate selectivity an reaction by directed mutagenesis lead to turnover rates. This work presents a novel approach predict conformation mutation along with effect on structure. The...

Protein folding -- the problem of predicting spatial structure a protein given its sequence amino-acids has attracted considerable research effort in biochemistry recent decades. In this work, we explore potential quantum computing to solve simplified version folding. More precisely, numerically investigate performance variational algorithm, Quantum Approximate Optimization Algorithm (QAOA), sampling low-energy conformations short peptides. We start by benchmarking algorithm on an even...