Tracing the substrate translocation mechanism in P-glycoprotein.

P-glycoprotein (Pgp) is a prototypical ATP-binding cassette (ABC) transporter of great biological and clinical significance.Pgp confers cancer multidrug resistance and mediates the bioavailability and pharmacokinetics of many drugs (Juliano and Ling, 1976; Ueda et al., 1986; Sharom, 2011).

Machine-guided path sampling to discover mechanisms of molecular self-organization.

Molecular self-organization driven by concerted many-body interactions produces the ordered structures that define both inanimate and living matter. Here we present an autonomous path sampling algorithm that integrates deep learning and transition path theory to discover the mechanism of molecular self-organization phenomena. The algorithm uses the outcome of newly initiated trajectories to construct, validate and-if needed-update quantitative mechanistic models.

Molecular Free Energies, Rates, and Mechanisms from Data-Efficient Path Sampling Simulations.

Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this limitation by collecting unbiased trajectories and capturing the relevant events.

Binding of SARS-CoV-2 Fusion Peptide to Host Endosome and Plasma Membrane.

During infection the SARS-CoV-2 virus fuses its viral envelope with cellular membranes of its human host. The viral spike (S) protein mediates both the initial contact with the host cell and the subsequent membrane fusion. Proteolytic cleavage of S at the S2' site exposes its fusion peptide (FP) as the new N-terminus.

Mechanism of the electroneutral sodium/proton antiporter PaNhaP from transition-path shooting.

Na/H antiporters exchange sodium ions and protons on opposite sides of lipid membranes. The electroneutral Na/H antiporter NhaP from archaea Pyrococcus abyssi (PaNhaP) is a functional homolog of the human Na/H exchanger NHE1, which is an important drug target. Here we resolve the Na and H transport cycle of PaNhaP by transition-path sampling.

Does volumetric measurement of cervical lymph nodes serve as an imaging biomarker for locoregional recurrence of oral squamous cell carcinoma?

Introduction: Recent studies highlighted the prognostic superiority of lymph node volume towards the conventional N Classification. However, data on the importance of neck lymph node volume, obtained by semiautomatic segmentation of CT images, do not exist for locoregional recurrence in patients with oral squamous cell carcinoma (OSCC).

Methods: Retrospective chart review of 100 patients, who were diagnosed and treated between 2006-2014.

Transition path sampling of rare events by shooting from the top.

Transition path sampling is a powerful tool in the study of rare events. Shooting trial trajectories from configurations along existing transition paths proved particularly efficient in the sampling of reactive trajectories. However, most shooting attempts tend not to result in transition paths, in particular in cases where the transition dynamics has diffusive character.