Research in Liao Y Chen Lab at UTSA

(supported with NIH grants, computed on Frontera, Lonestar 6, etc. and in-lab computers, experimented in BSE 3.104)

Refereed papers listed in ORCiD or NIH/NLM

Software: hSMD (hyper-steered molecular dynamics---steering without artifactual springs)
C++ modules, tcl and python scripts for running the dynamics and analyzing the data, and example studies.

Seeking quantitative insights into cell membrane specificities of neutral-solute transporters: Permeability of AQP1 in erythrocyte membrane is twofold larger than in POPE or POPC bilayer (DOI: 10.1039/D0RA03456H); AQP3 in erythrocyte membrane is a high affinity facilitator that conducts glycerol transport with unsaturable kinetics (DOI: 10.1039/D0RA05262K); GLUT1 in erythrocyte membrane acts differently than in a lipid bilayer without cell-specific asymmetry (Preprint DOI: 10.1101/787259, now published DOI: 10.1016/j.bbamem.2022.183975 ).
RBCm aqp3RBCm

Elucidating fluctuation-modulated structure-activity relationships (fmSAR): Subtle structural differences between AQP5 and AQP4 found to be responsible for substantial distinctions in their physiological roles (DOI: 10.1016/j.bbamem.2017.04.022 ); Gating dynamics of glucose transporter 1/3 (SLC2A1/3) (DOI: 10.1016/j.bbrc.2019.02.067, DOI: 10.1021/acschemneuro.8b00223 ).
aqp5vs4 glut1-ECgating

Quantifying protein interactions with chemical accuracy: DOI:10.1021/acs.jctc.5b00340. DOI:10.1016/j.bbrc.2017.04.084 . DOI:10.1021/acschemneuro.7b00409. Here are some movies in .gif.
protein-protein binding protein-protein binding

Computing absolute binding energy from hybrid steered molecular dynamics (hSMD) simulations: Brute force to accuracy, really? Come and see for yourself: Small molecule-protein binding problems: DOI 1: 10.1021/ct501162f . DOI 2: 10.1016/j.bbrc.2016.12.165 . DOI 3: 10.1016/j.bbamem.2019.01.008 . More binding problems are tabulated here.

hybrid Steered MD
hybrid Steered MD hybrid Steered MD

Finding water channel blockers: The widely used drug AZM binds weakly to the AQP4 channel entry vestibule. Is there a better way to block this and other water channels? DOI:10.1002/pro.2832, DOI:10.1576/JSIN.1000117, DOI:10.3389/fphy.2020.00119

In vitro evidence for the inhibitors: Human erythrocyte lyses under osmotic stress modulated by the inhibition of water channels natively expressed on the cell membrane. See, the inhibition is even visible:
See for yourself the colors red channel green channel blue channel

Interactions between nanoparticles in near-physiological aqueous solutions: (DOI:10.1039/C3CP54503B) (DOI:10.1039/C4CP05137H) (DOI:10.1021/acs.jpcb.5b09864) Langevin dynamics simulations are conducted for all-atom model systems under equilibrium and nonequilibrium conditions. Free-energy profiles are computed in terms of potential of mean force as a function of nanoparticle to nanoparticle separation distance.

Salt bridge formed between two nanoparticles

Some Movies Here.

Probing the inner workings of proteins in silico: Today's high-performance computing (HPC) enables us to model biological macromolecules with atomistic details. Running intensive in silico experiments on thousands of computing cores in parallel, we aim to elucidate the mechanistic details of how a channel protein functions to facilitate transport of water and other molecules across the cell membrane, providing insights that cannot be gained by in vitro experiments alone. (DOI: 10.1016/j.bbamem.2013.03.008) (DOI: 10.1016/j.jsb.2012.10.007) (DOI: 10.1016/j.bpc.2015.01.004) For example, alongside in vitro experiments, our recent in silico study ascertains the functional mechanism of aquaglyceroporin PfAQP (illustrated below). (PfAQP is the multi-functional channel protein in the plasma membrane of Plasmodium falciparum, the parasite causing the most severe form of malaria infecting millions of people every year.)

glycerol in and out of the pfaqp channel

Sampling transition paths: Many important transition/reaction events occur in the time scale of milliseconds while the underlying atomistic movements are in the time scale of picoseconds. Theoretical studies of these processes must overcome this vast separation of time scales that is ubiquitous in physical and biological systems. The two main approaches in the current literature are the transition state theory, which approximates transition/reaction as along the minimum energy path, and the transition path sampling approach, which samples various paths with appropriate statistical weights. Our research efforts in this area are to compute fluctuations around the minimum energy path and to develop efficient algorithms for transition path sampling.

Electronic transport in semiconductor nanostructures: At nanometer scale, the wave and particle natures of electrons concurrently manifest themselves to give rise to unique transport characteristics that define the forefront of electronic devices. Frequency response and noise characteristics are the central issues. Theoretical studies of various semiconductor nanostructures can be pursued based on the non-equilibrium Green’s function formulation that was proven successful for the double-barrier resonant-tunneling system.