Integrative Modeling in the Age of Machine Learning: A Summary of HADDOCK Strategies in CAPRI Rounds 47-55.

The HADDOCK team participated in CAPRI rounds 47-55 as server, manual predictor, and scorers. Throughout these CAPRI rounds, we used a plethora of computational strategies to predict the structure of protein complexes. Of the 10 targets comprising 24 interfaces, we achieved acceptable or better models for 3 targets in the human category and 1 in the server category.

Information-Driven Antibody-Antigen Modelling with HADDOCK.

In the recent years, therapeutic use of antibodies has seen a huge growth, "due to their inherent proprieties and technological advances in the methods used to study and characterize them. Effective design and engineering of antibodies for therapeutic purposes are heavily dependent on knowledge of the structural principles that regulate antibody-antigen interactions. Several experimental techniques such as X-ray crystallography, cryo-electron microscopy, NMR, or mutagenesis analysis can be applied, but these are usually expensive and time-consuming.

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment.

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers).

Native or Non-Native Protein-Protein Docking Models? Molecular Dynamics to the Rescue.

Molecular docking excels at creating a plethora of potential models of protein-protein complexes. To correctly distinguish the favorable, native-like models from the remaining ones remains, however, a challenge. We assessed here if a protocol based on molecular dynamics (MD) simulations would allow distinguishing native from non-native models to complement scoring functions used in docking.

Therapy of chronic hepatitis C in people who inject drugs: focus on adherence.

Background: Intravenous drug use (IVDU) represents the major factor of HCV transmission, but the treatment uptake among people who inject drugs (PWID) remains low owing to a false presumption of low efficacy. The aim of our study was to assess treatment efficacy in PWID and factors determining adherence to therapy.

Methods: A total of 278 consecutive patients starting DAA (direct-acting antivirals) therapy were included, divided into two groups: individuals with a history of IVDU, PWID group (N = 101) and the control group (N = 177) without a history of IVDU.

Redox Cofactor Rotates during Its Stepwise Decarboxylation: Molecular Mechanism of Conversion of Coproheme to Heme .

Coproheme decarboxylase (ChdC) catalyzes the last step in the heme biosynthesis pathway of monoderm bacteria with coproheme acting both as redox cofactor and substrate. Hydrogen peroxide mediates the stepwise decarboxylation of propionates 2 and 4 of coproheme. Here we present the crystal structures of coproheme-loaded ChdC from (LmChdC) and the three-propionate intermediate, for which the propionate at position 2 (p2) has been converted to a vinyl group and is rotated by 90° compared to the coproheme complex structure.

Free-Energy Calculations for Bioisosteric Modifications of A Adenosine Receptor Antagonists.

Adenosine receptors are a family of G protein-coupled receptors with increased attention as drug targets on different indications. We investigate the thermodynamics of ligand binding to the A adenosine receptor subtype, focusing on a recently reported series of diarylacetamidopyridine inhibitors via molecular dynamics simulations. With a combined approach of thermodynamic integration and one-step perturbation, we characterize the impact of the charge distribution in a central heteroaromatic ring on the binding affinity prediction.

Binding Modes and Metabolism of Caffeine.

A correct estimate of ligand binding modes and a ratio of their occupancies is crucial for calculations of binding free energies. The newly developed method BLUES combines molecular dynamics with nonequilibrium candidate Monte Carlo. Nonequilibrium candidate Monte Carlo generates a plethora of possible binding modes and molecular dynamics enables the system to relax.

Saturation Mutagenesis by Efficient Free-Energy Calculation.

Single-point mutations in proteins can greatly influence protein stability, binding affinity, protein function or its expression per se. Here, we present accurate and efficient predictions of the free energy of mutation of amino acids. We divided the complete mutational free energy into an uncharging step, which we approximate by a third-power fitting (TPF) approach, and an annihilation step, which we approximate using the one-step perturbation (OSP) method.

Free energy calculations on the stability of the 14-3-3ζ protein.

Mutations of cysteine are often introduced to e.g. avoid formation of non-physiological inter-molecular disulfide bridges in in-vitro experiments, or to maintain specificity in labeling experiments.

Correction: Native Phytoremediation Potential of Urtica dioica for Removal of PCBs and Heavy Metals Can Be Improved by Genetic Manipulations Using Constitutive CaMV 35S Promoter.

[This corrects the article DOI: 10.1371/journal.pone.

Serogroup and Clonal Characterization of Czech Invasive Neisseria meningitidis Strains Isolated from 1971 to 2015.

Background: This study presents antigenic and genetic characteristics of Neisseria meningitidis strains recovered from invasive meningococcal disease (IMD) in the Czech Republic in 1971-2015.

Material And Methods: A total of 1970 isolates from IMD, referred to the National Reference Laboratory for Meningococcal Infections in 1971-2015, were studied. All isolates were identified and characterized by conventional biochemical and serological tests.

Native Phytoremediation Potential of Urtica dioica for Removal of PCBs and Heavy Metals Can Be Improved by Genetic Manipulations Using Constitutive CaMV 35S Promoter.

Although stinging nettle (Urtica dioica) has been shown to reduce HM (heavy metal) content in soil, its wider phytoremediation potential has been neglected. Urtica dioica was cultivated in soils contaminated with HMs or polychlorinated biphenyls (PCBs). After four months, up to 33% of the less chlorinated biphenyls and 8% of HMs (Zn, Pb, Cd) had been removed.

Chemistry and Molecular Dynamics Simulations of Heme b-HemQ and Coproheme-HemQ.

Recently, a novel pathway for heme b biosynthesis in Gram-positive bacteria has been proposed. The final poorly understood step is catalyzed by an enzyme called HemQ and includes two decarboxylation reactions leading from coproheme to heme b. Coproheme has been suggested to act as both substrate and redox active cofactor in this reaction.

'Click chemistry' synthesis of 1-(α-D-mannopyranosyl)-1,2,3-triazoles for inhibition of α-mannosidases.

Three new triazole conjugates derived from d-mannose were synthesized and assayed in in vitro assays to investigate their ability to inhibit α-mannosidase enzymes from the glycoside hydrolase (GH) families 38 and 47. The triazole conjugates were more selective for a GH47 α-mannosidase (Aspergillus saitoi α1,2-mannosidase), showing inhibition at the micromolar level (IC50 values of 50-250 μM), and less potent towards GH38 mannosidases (IC50 values in the range of 0.5-6 mM towards jack bean α-mannosidase or Drosophila melanogaster lysosomal and Golgi α-mannosidases).