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Fullerenes, particularly C60, exhibit unique properties that make them promising candidates for various applications, including drug delivery and nanomedicine. However, their interactions with biomolecules, especially proteins, remain not fully understood. This study implements both explicit and implicit C60 models into the UNRES coarse-grained force field, enabling the investigation of fullerene–protein interactions without the need for restraints to stabilize protein structures. The UNRES force field offers computational efficiency, allowing for longer timescale simulations while maintaining accuracy. Five model proteins were studied: FK506 binding protein, HIV-1 protease, intestinal fatty acid binding protein, PCB-binding protein, and hen egg-white lysozyme. Molecular dynamics simulations were performed with and without C60 to assess protein stability and investigate the impact of fullerene interactions. Analysis of contact probabilities reveals distinct interaction patterns for each protein. FK506 binding protein (1FKF) shows specific binding sites, while intestinal fatty acid binding protein (1ICN) and uteroglobin (1UTR) exhibit more generalized interactions. The explicit C60 model shows good agreement with all-atom simulations in predicting protein flexibility, the position of C60 in the binding pocket, and the estimation of effective binding energies. The integration of explicit and implicit C60 models into the UNRES force field, coupled with recent advances in coarse-grained modeling and multiscale approaches, provides a powerful framework for investigating protein–nanoparticle interactions at biologically relevant scales without the need to use restraints stabilizing the protein, thus allowing for large conformational changes to occur. These computational tools, in synergy with experimental techniques, can aid in understanding the mechanisms and consequences of nanoparticle–biomolecule interactions, guiding the design of nanomaterials for biomedical applications.

Abstract Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.

Abstract Background The aim of the present paper is to assess the gait pattern of patients with Peripheral Artery Disease (PAD). A more specific aim is to compare the gait pattern of PAD patients before and after the appearance of intermittent claudication symptoms. Methods The study involved 34 PAD patients with a claudication distance ≥200 m and 20 participants without PAD, who formed the control group. The gait pattern of PAD patients was assessed twice: before the appearance of intermittent claudication symptoms (pain-free conditions) and after the appearance of intermittent claudication symptoms (pain conditions). Results Compared to the control group, PAD patients presented a statistically significant decrease in step length both during pain-free conditions (52.6 ± 12.5 vs. 72.8 ± 18.5 cm, p = 0.008) and in pain conditions (53.3 ± 13.3 vs. 72.8 ± 18.5 cm, p = 0.006). As for the remaining spatiotemporal parameters, there were no differences observed between the patient group and the controls. Intermittent claudication symptom induced by the walking test on the treadmill did not bring about any new abnormalities in the gait pattern or intensify the existing abnormalities of the gait. Conclusions PAD patients have a tendency to shorten their step length regardless of the presence of intermittent claudication.

Disulfide bonds, despite the advances of the computational methods, are underrepresented in theoretical chemistry and the role of disulfide bonds is often diminished in bioinformatical studies. Most of the molecular modeling tools do not allow studying the process of disulfide bond formation and breaking, which is equally important as the sole presence of disulfide bonds in proteins and peptides. The UNRES (UNited RESidue) coarse-grained force field allows treating disulfide bonds in two ways: as static (formed or broken in the simulation) or dynamic (all specified cysteine residues can form and break disulfide bonds during simulation). The comparison between those two approaches of disulfide-bond treatment is presented for protein folding on the example of four small β- and α+β proteins with one, two, three and four disulfide bonds. The results clearly show that proper disulfide bond treatment is important in simulations and significantly enhances the quality of folded structures.

Even though most of the existing studies of gold nanoparticles indicate that they are safe to use, some researchers show that specific forms of nanoparticles (e.g. nanorods) are able to destroy the cell membrane and very small nanoparticles (below 37 nm in diameter) in high concentration have been deadly for mice. We used the Amber12 package to perform a series of molecular dynamics (MD) simulations of gold nanoparticles with various small proteins important for the human body and a DNA molecule to determine the interactions and consequently the possible toxicity of gold clusters. Lennard-Jones interactions were used to simulate the behavior of gold nanoparticles with biomacromolecules in water with an optimal set of parameters (selected based on a comparison of MD structures and structures computed by DFT). Gold nanoparticle structures were obtained as a result of MD simulations from an initial structure, where gold atoms were at a distance of 10˚A from one another. A predicted BDNA structure of a palindromic sequence ‘CGCATGAGTACGC’ and a 2JYK molecule were used as representatives of the DNA molecule. The preliminary results show that, in particular small gold nanoparticles, interact strongly with proteins and DNA by creating stable complexes, which can then cause harmful reactions to the human body when present in high concentration.

Toll-like receptors (TLRs) are a group of proteins which play a crucial role in the innate immune system. The main function of TLRs is to recognize structurally conserved molecules, which are inserted to the organism of the host by microbes, and then to activate the immune response. Current development of drugs is often connected not only with the drug itself, but also with the way it is delivered into the human body to interact directly with the source of the problem. Carbon nanostructures, particularly nanotubes, are one of the carrier molecules of the future. However, there is still no knowledge about the exact mechanisms of toxicity and possible interactions with macromolecules, such as proteins. In our study we tried to determine, if the nanotubes could interfere with the innate immune system by interacting with TLRs. For this purpose, we used the following TLR structures downloaded from the RCSB Protein Data Bank: TLR2 (3A7C), TLR4/MD (3FXI), TLR5 (3V47), TLR3 (2A0Z), and the complexes of TLR1/TLR2 (2Z7X) and TLR2/TLR6 (3A79). The preliminary results of our Steered Molecular Dynamics (SMD) simulations have shown that nanotubes interact very strongly with the binding pockets of some receptors (e.g. TLR2), which results in their binding to these sites without substantial use of the external force.