Yunlong Liu - Academia.edu (original) (raw)
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Papers by Yunlong Liu
Proteins, which are essentially linear polymers of amino acid residues, perform a tremendous vari... more Proteins, which are essentially linear polymers of amino acid residues, perform a tremendous variety of functions, including catalyzing biochemical reactions, replicating genetic information, transporting molecules, constructing cell architecture, and transducing signals in the microscopic milieu of cells and the interstitial fluid. Such linear chains of residues undergo complicated folding processes to form biologically active 3-dimensional structures as they are translated. Since the first protein structure of myoglobin was determined using X-ray crystallography in 1958, biophysicists have been making continuous efforts to understand the associations between protein structures and their functions. Unfortunately, only static snapshots and limited dynamics of proteins at atomic-level resolution are available with the experimental approaches developed so far, which precludes a complete biophysical and temporal understanding of protein mechanisms in the context of the microscopic bioc...
Proceedings of the National Academy of Sciences of the United States of America, Sep 25, 2016
The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid-the first step in... more The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid-the first step in thyroid hormone biosynthesis-with a 2 Na(+): 1 I(-) stoichiometry. The two Na(+) binding sites (Na1 and Na2) and the I(-) binding site interact allosterically: when Na(+) binds to a Na(+) site, the affinity of NIS for the other Na(+) and for I(-) increases significantly. In all Na(+)-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na(+) ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues-S66, D191, Q194, and Q263-are also involved in Na(+) coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I(-) These r...
ArXiv, 2018
Recent developments in specialized computer hardware have greatly accelerated atomic level Molecu... more Recent developments in specialized computer hardware have greatly accelerated atomic level Molecular Dynamics (MD) simulations. A single GPU-attached cluster is capable of producing microsecond-length trajectories in reasonable amounts of time. Multiple protein states and a large number of microstates associated with folding and with the function of the protein can be observed as conformations sampled in the trajectories. Clustering those conformations, however, is needed for identifying protein states, evaluating transition rates and understanding protein behavior. In this paper, we propose a novel data-driven generative conformation clustering method based on the adversarial autoencoder (AAE) and provide the associated software implementation Cong. The method was tested using a 208 microseconds MD simulation of the fast-folding peptide Trp-Cage (20 residues) obtained from the D.E. Shaw Research Group. The proposed clustering algorithm identifies many of the salient features of the...
Proteins, which are essentially linear polymers of amino acid residues, perform a tremendous vari... more Proteins, which are essentially linear polymers of amino acid residues, perform a tremendous variety of functions, including catalyzing biochemical reactions, replicating genetic information, transporting molecules, constructing cell architecture, and transducing signals in the microscopic milieu of cells and the interstitial fluid. Such linear chains of residues undergo complicated folding processes to form biologically active 3-dimensional structures as they are translated. Since the first protein structure of myoglobin was determined using X-ray crystallography in 1958, biophysicists have been making continuous efforts to understand the associations between protein structures and their functions. Unfortunately, only static snapshots and limited dynamics of proteins at atomic-level resolution are available with the experimental approaches developed so far, which precludes a complete biophysical and temporal understanding of protein mechanisms in the context of the microscopic bioc...
Proceedings of the National Academy of Sciences of the United States of America, Sep 25, 2016
The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid-the first step in... more The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid-the first step in thyroid hormone biosynthesis-with a 2 Na(+): 1 I(-) stoichiometry. The two Na(+) binding sites (Na1 and Na2) and the I(-) binding site interact allosterically: when Na(+) binds to a Na(+) site, the affinity of NIS for the other Na(+) and for I(-) increases significantly. In all Na(+)-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na(+) ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues-S66, D191, Q194, and Q263-are also involved in Na(+) coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I(-) These r...
ArXiv, 2018
Recent developments in specialized computer hardware have greatly accelerated atomic level Molecu... more Recent developments in specialized computer hardware have greatly accelerated atomic level Molecular Dynamics (MD) simulations. A single GPU-attached cluster is capable of producing microsecond-length trajectories in reasonable amounts of time. Multiple protein states and a large number of microstates associated with folding and with the function of the protein can be observed as conformations sampled in the trajectories. Clustering those conformations, however, is needed for identifying protein states, evaluating transition rates and understanding protein behavior. In this paper, we propose a novel data-driven generative conformation clustering method based on the adversarial autoencoder (AAE) and provide the associated software implementation Cong. The method was tested using a 208 microseconds MD simulation of the fast-folding peptide Trp-Cage (20 residues) obtained from the D.E. Shaw Research Group. The proposed clustering algorithm identifies many of the salient features of the...