Computer-Guided Navigation System Efficiency Evaluation Using Surgical Instruments for Spinal Fusion.

Background: Navigation surgical systems have been widely used in spinal fusion to ensure accuracy and safety during pedicle screw insertion.

Methods: The research was performed under laboratory conditions, using stereotactic navigation, surgical instruments for spinal fusion, development of additional devices and software. During the experiments, all stages of the computed tomography-guided navigation system use were performed-preoperative preparation of patient data and planning to provide visual control of the navigation of surgical instruments during the insertion of screws.

Preparation of Antimicrobial Agents: From Interpolyelectrolyte Complexes to Silver-Containing Metal-Polymer Complexes and Nanocomposites.

In order to control pathogenic microorganisms, three polymer compositions were prepared and tested. First, a water-soluble positively charged polycomplex was synthesized via the electrostatic binding of anionic polyacrylic acid to an excess of polyethylenimine to enhance the biocidal activity of the polycation. Second, an aqueous solution of AgNO was added to the polycomplex, thus forming a ternary polycation-polyanion-Ag complex with an additional antimicrobial effect.

Binding of Inhibitors to Nuclear Localization Signal Peptide from Venezuelan Equine Encephalitis Virus Capsid Protein Explored with All-Atom Replica Exchange Molecular Dynamics.

Several small molecule inhibitors have been designed to block binding of the Venezuelan equine encephalitis virus (VEEV) nuclear localization signal (NLS) sequence to the importin-α nuclear transport protein. To probe the inhibition mechanism on a molecular level, we used all-atom explicit water replica exchange molecular dynamics to study the binding of two inhibitors, I1 and I2, to the coreNLS peptide, representing the core fragment of the VEEV NLS sequence. Our objective was to evaluate the possibility of masking wherein binding of these inhibitors to the coreNLS occurs prior to its binding to importin-α.

Competitive Binding of Viral Nuclear Localization Signal Peptide and Inhibitor Ligands to Importin-α Nuclear Transport Protein.

Venezuelan equine encephalitis virus (VEEV) is a highly virulent pathogen whose nuclear localization signal (NLS) sequence from capsid protein binds to the host importin-α transport protein and blocks nuclear import. We studied the molecular mechanisms by which two small ligands, termed I1 and I2, interfere with the binding of VEEV's NLS peptide to importin-α protein. To this end, we performed all-atom replica exchange molecular dynamics simulations probing the competitive binding of the VEEV coreNLS peptide and I1 or I2 ligand to the importin-α major NLS binding site.

Binding and dimerization of PGLa peptides in anionic lipid bilayer studied by replica exchange molecular dynamics.

The 21-residue PGLa peptide is well known for antimicrobial activity attributed to its ability to compromize bacterial membranes. Using all-atom explicit solvent replica exchange molecular dynamics with solute tempering, we studied PGLa binding to a model anionic DMPC/DMPG bilayer at the high peptide:lipid ratio that promotes PGLa dimerization (a two peptides per leaflet system). As a reference we used our previous simulations at the low peptide:lipid ratio (a one peptide per leaflet system).

Replica Exchange with Hybrid Tempering Efficiently Samples PGLa Peptide Binding to Anionic Bilayer.

We evaluated the utility of a variant of the replica exchange method, a replica exchange with hybrid tempering (REHT), for all-atom explicit water biomolecular simulations and compared it with a more traditional replica exchange with the solute tempering (REST) algorithm. As a test system, we selected a 21-mer antimicrobial peptide PGLa binding to an anionic DMPC/DMPG lipid bilayer. Application of REHT revealed the following binding mechanism.

Binding of viral nuclear localization signal peptides to importin-α nuclear transport protein.

Using all-atom replica-exchange molecular dynamics simulations, we mapped the mechanisms of binding of the nuclear localization signal (NLS) sequence from Venezuelan equine encephalitis virus (VEEV) capsid protein to importin-α (impα) transport protein. Our objective was to identify the VEEV NLS sequence fragment that confers native, experimentally resolved binding to impα as well as to study associated binding energetics and conformational ensembles. The two selected VEEV NLS peptide fragments, KKPK and KKPKKE, show strikingly different binding mechanisms.

Can Free Energy Perturbation Simulations Coupled with Replica-Exchange Molecular Dynamics Study Ligands with Distributed Binding Sites?

Free energy perturbation coupled with replica exchange with solute tempering (FEP/REST) offers a rigorous approach to compute relative free energy changes for ligands. To determine the applicability of FEP/REST for the ligands with distributed binding poses, we considered two alchemical transformations involving three putative inhibitors I0, I1, and I2 of the Venezuelan equine encephalitis virus nuclear localization signal sequence binding to the importin-α (impα) transporter protein. I0 → I1 and I0 → I2 transformations, respectively, increase or decrease the polarity of the parent molecule.

Assessment of experimental OpenCV tracking algorithms for ultrasound videos.

This study aims to compare the tracking algorithms provided by the OpenCV library to use on ultrasound video. Despite the widespread application of this computer vision library, few works describe the attempts to use it to track the movement of liver tumors on ultrasound video. Movements of the neoplasms caused by the patient`s breath interfere with the positioning of the instruments during the process of biopsy and radio-frequency ablation.

Binding of Venezuelan Equine Encephalitis Virus Inhibitors to Importin-α Receptors Explored with All-Atom Replica Exchange Molecular Dynamics.

Although Venezuelan equine encephalitis virus (VEEV) is a life-threatening pathogen with a capacity for epidemic outbreaks, there are no FDA-approved VEEV antivirals for humans. VEEV cytotoxicity is partially attributed to the formation of a tetrameric complex between the VEEV capsid protein, the nuclear import proteins importin-α and importin-β, and the nuclear export protein CRM1, which together block trafficking through the nuclear pore complex. Experimental studies have identified small molecules from the CL6662 scaffold as potential inhibitors of the viral nuclear localization signal (NLS) sequence binding to importin-α.

Modular robot interface for a smart operating theater.

This paper discusses the architecture and implementation of a modular component of the smart operating theater digital twin, designed to control robotic equipment-the robot interface module. This interface is designed to ensure equipment operation both in a real smart operating theater and in the virtual space of its digital twin-the computer simulation. Using such an interface in the digital twin will make it possible to use it in computer-assisted training of surgeons, preliminary planning, post-analysis, and simulation, preceding the operation of real equipment.

Lysine Acetylation Changes the Mechanism of Aβ25-35 Peptide Binding and Dimerization in the DMPC Bilayer.

The impact of Lys28 acetylation on Alzheimer's Aβ peptide binding to the lipid bilayer has not been previously studied, either experimentally or computationally. To probe this common post-translational modification, we performed all-atom replica exchange molecular dynamics simulations targeting binding and aggregation of acetylated acAβ25-35 peptide within the DMPC bilayer. Using the unmodified Aβ25-35 studied previously as a reference, our results can be summarized as follows.

Transmembrane Aggregation of Aβ10-40 Peptides in an Anionic Lipid Bilayer.

Using the all-atom model and 10 μs serial replica-exchange molecular dynamics (SREMD), we investigated the binding of Alzheimer's Aβ10-40 peptides to the anionic dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) lipid bilayer. Our objective was to probe transmembrane Aβ10-40 aggregation and to test the utility of SREMD. Our results are threefold.

Preparation of Biocidal Nanocomposites in X-ray Irradiated Interpolyelectolyte Complexes of Polyacrylic Acid and Polyethylenimine with Ag-Ions.

Due to the presence of cationic units interpolyelectrolyte complexes (IPECs) can be used as a universal basis for preparation of biocidal coatings on different surfaces. Metallopolymer nanocomposites were successfully synthesized in irradiated solutions of polyacrylic acid (PAA) and polyethylenimine (PEI), and dispersions of non-stoichiometric IPECs of PAA-PEI containing silver ions. The data from turbidimetric titration and dynamic light scattering showed that pH 6 is the optimal value for obtaining IPECs.

Mechanisms of Binding of Antimicrobial Peptide PGLa to DMPC/DMPG Membrane.

PGLa belongs to a class of antimicrobial peptides showing strong affinity to anionic bacterial membranes. Using all-atom explicit solvent replica exchange molecular dynamics with solute tempering, we studied binding of PGLa to a model anionic dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) bilayer. Due to a strong hydrophobic moment, PGLa upon binding adopts a helical structure and two distinct bound states separated by a significant free energy barrier.

Machine learning-based prediction of drug and ligand binding in BCL-2 variants through molecular dynamics.

Venetoclax is a BH3 (BCL-2 Homology 3) mimetic used to treat leukemia and lymphoma by inhibiting the anti-apoptotic BCL-2 protein thereby promoting apoptosis of cancerous cells. Acquired resistance to Venetoclax via specific variants in BCL-2 is a major problem for the successful treatment of cancer patients. Replica exchange molecular dynamics (REMD) simulations combined with machine learning were used to define the average structure of variants in aqueous solution to predict changes in drug and ligand binding in BCL-2 variants.

Speckle-Based Sensing of Microscopic Dynamics in Expanding Polymer Foams: Application of the Stacked Speckle History Technique.

Microscopic structural rearrangements in expanding polylactide foams were probed using multiple dynamic scattering of laser radiation in the foam volume. Formation and subsequent expansion of polylactide foams was provided by a rapid or slow depressurization of the "plasticized polylactide-supercritical carbon dioxide" system. Dynamic speckles induced by a multiple scattering of laser radiation in the expanding foam were analyzed using the stacked speckle history technique, which is based on a joint mapping of spatial-temporal dynamics of evolving speckle patterns.

Data Mining of Molecular Simulations Suggest Key Amino Acid Residues for Aggregation, Signaling and Drug Action.

Alzheimer's disease, the most common form of dementia, currently has no cure. There are only temporary treatments that reduce symptoms and the progression of the disease. Alzheimer's disease is characterized by the prevalence of plaques of aggregated amyloid β (Aβ) peptide.

Met35 Oxidation Hinders Aβ25-35 Peptide Aggregation within the Dimyristoylphosphatidylcholine Bilayer.

Using all-atom explicit solvent replica exchange molecular dynamics simulations, we studied the aggregation of oxidized (ox) Aβ25-35 peptides into dimers mediated by the zwitterionic dimyristoylphosphatidylcholine (DMPC) lipid bilayer. By comparing oxAβ25-35 aggregation with that observed for reduced and phosphorylated Aβ25-35 peptides, we elucidated plausible impact of post-translational modifications on cytotoxicity of Aβ peptides involved in Alzheimer's disease. We found that Met35 oxidation reduces helical propensity in oxAβ25-35 peptides bound to the lipid bilayer and enhances backbone fluctuations.

The concept of spatial motion restriction zones in a robot-assisted surgical system.

The development of robotics and medicine in recent years leads to increasing mutual integration of these two disciplines. The use of specialized robotic solutions in medicine poses new challenges, including the issue of safety. The paper analyzes existing solutions aimed at improving safety in medical robotics.

Partitioning of Aβ Peptide Fragments into Blood-Brain Barrier Mimetic Bilayer.

We used all-atom replica-exchange umbrella sampling molecular dynamics simulations to investigate the partitioning of the charged tetrapeptide KLVF and its neutral apolar counterpart VVIA into the blood-brain barrier (BBB)-mimetic bilayer. Our findings allowed us to reconstruct the partitioning mechanism for these two Aβ peptide fragments. Despite dissimilar sequences, their permeation shares significant common features.

Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations.

Distinct missense mutations in a specific gene have been associated with different diseases as well as differing severity of a disease. Current computational methods predict the potential pathogenicity of a missense variant but fail to differentiate between separate disease or severity phenotypes. We have developed a method to overcome this limitation by applying machine learning to features extracted from molecular dynamics simulations, creating a way to predict the effect of novel genetic variants in causing a disease, drug resistance, or another specific trait.