Extended Sampling of Macromolecular Conformations from Uniformly Distributed Points on Multidimensional Normal Mode Hyperspheres.

Proteins are dynamic entities that adopt diverse conformations, which play a pivotal role in their function. Understanding these conformations is essential, and protein collective motions, particularly those captured by normal mode (NM) and their linear combinations, provide a robust means for conformational sampling. This work introduces a novel approach to obtaining a uniformly oriented set of a given number of lowest frequency NM combined vectors and generating harmonically equidistant restrained structures along them.

MDFF_NM: Improved Molecular Dynamics Flexible Fitting into Cryo-EM Density Maps with a Multireplica Normal Mode-Based Search.

Molecular Dynamics Flexible Fitting (MDFF) is a widely used tool to refine high-resolution structures into cryo-EM density maps. Despite many successful applications, MDFF is still limited by its high computational cost, overfitting, accuracy, and performance issues due to entrapment within wrong local minima. Modern ensemble-based MDFF tools have generated promising results in the past decade.

From ionic clusters dynamics to network constraints in ionic polymer solutions.

Physical networks formed by ionizable polymers with ionic clusters as crosslinks are controlled by coupled dynamics that transcend from ionic clusters through chain motion to macroscopic response. Here, the coupled dynamics, across length scales, from the ionic clusters to the networks in toluene swollen polystyrene sulfonate networks, were directly correlated, as the electrostatic environment of the physical crosslinks was altered. The multiscale insight is attained by coupling neutron spin echo measurements with molecular dynamics simulations, carried out to times typical of relaxation of polymers in solutions.

From Molecular Constraints to Macroscopic Dynamics in Associative Networks Formed by Ionizable Polymers: A Neutron Spin Echo and Molecular Dynamics Simulations Study.

The association of ionizable polymers strongly affects their motion in solutions, where the constraints arising from clustering of the ionizable groups alter the macroscopic dynamics. The interrelation between the motion on multiple length and time scales is fundamental to a broad range of complex fluids including physical networks, gels, and polymer-nanoparticle complexes where long-lived associations control their structure and dynamics. Using neutron spin echo and fully atomistic, multimillion atom molecular dynamics (MD) simulations carried out to times comparable to that of chain segmental motion, the current study resolves the dynamics of networks formed by suflonated polystryene solutions for sulfonation fractions 0 ≤ ≤ 0.

Assessment of Efficacy and Safety of Zagotenemab: Results From PERISCOPE-ALZ, a Phase 2 Study in Early Symptomatic Alzheimer Disease.

Background And Objectives: Zagotenemab (LY3303560), a monoclonal antibody that preferentially targets misfolded, extracellular, aggregated tau, was assessed in the PERISCOPE-ALZ phase 2 study to determine its ability to slow cognitive and functional decline relative to placebo in early symptomatic Alzheimer disease (AD).

Methods: Participants were enrolled across 56 sites in North America and Japan. Key eligibility criteria included age of 60-85 years, Mini-Mental State Examination score of 20-28, and intermediate levels of brain tau on PET imaging.