Qinghua Liao

University of Barcelona | UB · Institute of Theoretical and Computational Chemistry (IQTCUB)

Microbes utilize polysaccharides to protect their surfaces and build biofilms, whereas metazoans employ large mucins densely decorated with O-glycans to protect surfaces and keep microbes at a distance. However, gut microbes in mucus also feed on host mucins, thus imposing a need for continuous renewal to maintain protection, clearance and mucus ho...

3-Phosphoglycerate Dehydrogenase (PHGDH) is primarily known for catalyzing the oxidation of 3-phosphoglycerate (3PG) to 3-phosphohydroxypyvurate (3PHP) by reducing NAD + to NADH, an important step during L-serine biosynthesis in human cells, however, it also catalyzes the reduction of α-ketoglutarate (α-KG) into 2-Hydroxyglutarate (2-HG), a carcino...

Mucinases of human gut bacteria cleave peptide bonds in mucins strictly depending on the presence of neighboring O-glycans. The Akkermansia muciniphila AM0627 mucinase cleaves specifically in between contiguous (bis) O-glycans of defined truncated structures, suggesting that this enzyme may recognize clustered O-glycan patches. Here, we report the...

DNA-binding proteins play an important role in gene regulation and cellular function. The transcription factors MarA and Rob are two homologous members of the AraC/XylS family that regulate multidrug resistance. They share a common DNA-binding domain, and Rob possesses an additional C-terminal domain that permits binding of low-molecular weight eff...

div> DNA-binding proteins play an important role in gene regulation and cellular function. The transcription factors MarA and Rob are two homologous members of the AraC/XylS family that regulate multidrug resistance. They share a common DNA-binding domain, and Rob possesses an additional C-terminal domain that permits binding of low-molecular wei...

Molecular dynamics simulation is a powerful computational technique to study biomolecular systems, which complements experiments by providing insights into the structural dynamics relevant to biological functions at atomic scale. It can also be used to calculate the free energy landscapes of the conformational transitions to better understand the f...

Evolutionary trajectories are deemed largely irreversible. In a newly diverged protein, reversion of mutations that led to the functional switch typically results in loss of both the new and ancestral functions. Nonetheless, evolutionary transitions where reversions are viable have also been described. The structural and mechanistic causes of rever...

Recent years have witnessed an explosion of interest in computational studies of DNA binding proteins, including both coarse grained and atomistic simulations of transcription factor-DNA recognition, in order to understand how these transcription factors recognize their binding sites on the DNA with such exquisite specificity. The present study per...

p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px 'Helvetica Neue'} Recent years have witnessed an explosion of interest in computational studies of DNA binding proteins, including both coarse grained and atomistic simulations of transcription factor-DNA recognition, in order to understand how these transcription factors recognize their binding...

Conformational changes are crucial for the catalytic action of many enzymes. A prototypical and well-studied example is loop opening and closure in triosephosphate isomerase (TIM), which is thought to determine the rate of catalytic turnover in many circumstances. Specifically, TIM loop 6 ‘grips’ the phosphodianion of the substrate and, together wi...

In light of the high affinity of Cu²⁺ for Alzheimer’s Aβ1−42 and its ability to subsequently catalyze the formation of radicals, we examine the effects of Cu²⁺ binding, Aβ oxidation, and an acidic environment on the conformational dynamics of the smallest Aβ²⁺ oligomer, the Aβ²⁺ dimer. Transition networks calculated from Hamiltonian replica exchang...

The amphiphilic nature of the amyloid-β (Aβ) peptide associated with Alzheimer’s disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of Aβ(1-40) in the p...

We have previously performed empirical valence bond calculations of the kinetic activation barriers, ∆G‡calc, for the deprotonation of complexes between TIM and the whole substrate glyceraldehyde-3-phosphate (GAP, Kulkarni et al. J. Am. Chem. Soc. 2017 , 139, 10514-10525). We now extend this work to also study the deprotonation of the substrate pie...

[small beta]-phosphoglucomutase ([small beta]-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of [small beta]-glucose-1-phosphate to [small beta]-glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mec...

One of the the main research topics related to Alzheimer’s disease is the aggregation of the amyloid-β peptide, which was shown to follow different pathways for the two major alloforms of the peptide, Aβ40 and the more toxic Aβ42. Experimental studies emphasized that oligomers of specific sizes appear in the early aggregation process in different q...

Modeling metalloproteins often requires classical molecular dynamics (MD) simulations in order to capture their relevant motions, which in turn necessitates reliable descriptions of the metal centers involved. One of the most successful approaches to date is provided by the “cationic dummy model”, where the positive charge of the metal ion is trans...

Triosephosphate isomerase (TIM) is a proficient catalyst of the reversible isomerization of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde phosphate (GAP), via general base catalysis by E165. Historically, this enzyme has been an extremely important model system for understanding the fundamentals of biological catalysis. TIM is activated thr...

Amyloid-β (Aβ) is a natively unfolded peptide found in all Alzheimer's disease patients as the major component of fibrillar plaques, which are recognized as an important pathological hallmark in Alzheimer's disease. The binding of copper to Aβ increases its neurotoxicity, as Cu²⁺ causes Aβ to become redox active and decreases the lag time associate...

Metal ions are both ubiquitous to and crucial in biology. In classical simulations, they are typically described as simple van der Waals spheres, making it difficult to provide reliable force field descriptions for them. An alternative is given by nonbonded dummy models, in which the central metal atom is surrounded by dummy particles that each car...

Phosphoglycerate mutase catalyzes the interconversion between 2-phosphoglycerate and 3-phosphoglycerate in the glycolytic and gluconeogenic pathways. They exist in two unrelated forms, that is either cofactor (2,3-diphosphoglycerate) dependent or cofactor-independent. These two enzymes have no similarity in amino acid sequence, tertiary structure,...

Retinoid X receptors (RXRα, β and γ) are recently known to be cancer chemotherapies targets. The ligand binding domains of RXRs have been crystallized, but the information of RXRγ ligand binding site is not yet available due to the lack of liganded complex. A thorough understanding of the ligand binding sites is essential to study RXRs and may resu...

EGFR is the cell-surface receptor. Its overexpression or overactivity has been associated with a number of cancers, including breast, lung, ovarian, and anal cancers. Many therapeutic approaches are aimed at the EGFR. A series of 2, 7-diamino-thiazolo [4,5-d] pyrimidine analogues are among the most highly potent and selective inhibitors of EGFR des...

Extensive studies suggest direct links between cholesteryl ester transfer protein (CETP), high-density lipoproteins-cholesterol level and cardiovascular diseases. Many therapeutic approaches are aimed at the CETP. A series of N, N-disubstituted-trifluoro-3-amino-2-propanol analogues are among the most highly potent and selective inhibitors of CETP...

Corticotropin-releasing factor (CRF) is a neuropeptide that falls into the broad spectrum of having neurotransmitter/neurohormonal/neuromodulator activities. The design and synthesis of low molecular weight non-peptide antagonists for the CRF receptors is a very important area of research as they can be employed in the treatment of a wide variety o...