Distinct roles of the major binding residues in the cation-binding pocket of the melibiose transporter MelB.

Salmonella enterica serovar Typhimurium melibiose permease (MelB) is a prototype of the major facilitator superfamily (MFS) transporters, which play important roles in human health and diseases. MelB catalyzed the symport of galactosides with Na, Li, or H but prefers the coupling with Na. Previously, we determined the structures of the inward- and outward-facing conformation of MelB and the molecular recognition for galactoside and Na.

Distinct roles of the major binding residues in the cation-binding pocket of MelB.

serovar Typhimurium melibiose permease (MelB) is a prototype of the major facilitator superfamily (MFS) transporters, which play important roles in human health and diseases. MelB catalyzed the symport of galactosides with either H, Li, or Na, but prefers the coupling with Na. Previously, we determined the structures of the inward- and outward-facing conformation of MelB, as well as the molecular recognition for galactoside and Na.

Mobile barrier mechanisms for Na-coupled symport in an MFS sugar transporter.

While many 3D structures of cation-coupled transporters have been determined, the mechanistic details governing the obligatory coupling and functional regulations still remain elusive. The bacterial melibiose transporter (MelB) is a prototype of major facilitator superfamily transporters. With a conformation-selective nanobody, we determined a low-sugar affinity inward-facing Na-bound cryoEM structure.

Mobile barrier mechanisms for Na-coupled symport in an MFS sugar transporter.

While many 3D structures of cation-coupled transporters have been determined, the mechanistic details governing the obligatory coupling and functional regulations still remain elusive. The bacterial melibiose transporter (MelB) is a prototype of the Na-coupled major facilitator superfamily transporters. With a conformational nanobody (Nb), we determined a low-sugar affinity inward-facing Na-bound cryoEM structure.

On the Simulation of Thermal Isomerization of Molecular Photoswitches in Biological Systems.

Molecular photoswitches offer precise, reversible photocontrol over biomolecular functions and are promising light-regulated drug candidates with minimal side effects. Quantifying thermal isomerization rates of photoswitches in their target biomolecules is essential for fine-tuning their light-controlled drug activity. However, the effects of protein binding on isomerization kinetics remain poorly understood, and simulations are crucial for filling this gap.

Multiscale simulation unravels the light-regulated reversible inhibition of dihydrofolate reductase by phototrexate.

Molecular photoswitches are widely used in photopharmacology, where the biomolecular functions are photo-controlled reversibly with high spatiotemporal precision. Despite the success of this field, it remains elusive how the protein environment modulates the photochemical properties of photoswitches. Understanding this fundamental question is critical for designing more effective light-regulated drugs with mitigated side effects.

Effects of Enzyme-Ligand Interactions on the Photoisomerization of a Light-Regulated Chemotherapeutic Drug.

Molecular photoswitches permit using light to control protein activity with high spatiotemporal resolutions, thereby alleviating the side effects of conventional chemotherapy. However, due to the challenges in probing ultrafast photoisomerization reactions in biological environments, it remains elusive how the protein influences the photochemistry of the photoswitches, which hampers the rational design of light-regulated therapeutics. To overcome this challenge, we employed first-principles nonadiabatic dynamics simulations to characterize the photodynamics of the phototrexate (PTX), a recently developed photoswitchable anticancer chemotherapeutic that reversibly inhibits its target enzyme dihydrofolate reductase (DHFR).

Protein confinement fine-tunes aggregation-induced emission in human serum albumin.

Luminogens exhibiting aggregation-induced-emission characteristics (AIEgens) have been designed as sensitive biosensors thanks to their "turn-on" fluorescence upon target binding. However, their AIE mechanism in biomolecules remains elusive except for the qualitative picture of restricted intramolecular motions. In this work, we employed simulations to investigate the AIE mechanism of two tetraphenylethylene derivatives recently developed for sensitive detection of human serum albumin (HSA) in biological fluids.

A bioprinted composite hydrogel with controlled shear stress on cells.

In recent decades, three dimensional (3D) bio-printing technology has found widespread use in tissue engineering applications. The aim of this study is to scrutinize different parameters of the bioprinter - with the help of simulation software - to print a hydrogel so much so that avoid high amounts of shear stress which is detrimental for cell viability and cell proliferation. The results have led to the combination of percentages collagen:alginate:gelatin (1:4:8)% as the best condition which makes sol-gel transition at room temperature possible.