New JACS Communication on fluorinated peptoids

posted Feb 19, 2019, 11:48 AM by Vincent Voelz

Congrats to lab members Matt Hurley and Guangfeng Zhou for their work on this JACS Communication paper, now in print!  In this collaboration with Steven Cobb's group at Durham University, UK,  we modeled the structure and dynamics of fluorinated α-peptoids, a promising new peptoid architecture for synthetic helical-scaffold peptidomimetics.  You can read the paper here:

Gimenez, D., Zhou, G., Hurley, M. F. D., Aguilar, J. A., Voelz, V. A., & Cobb, S. L. (2019). Fluorinated Aromatic Monomers as Building Blocks To Control α-Peptoid Conformation and Structure. Journal of the American Chemical Society (Communication).

New paper on PAH is an Editors' Pick at Journal of Biological Chemistry

posted Jan 3, 2019, 7:06 AM by Vincent Voelz   [ updated Jan 5, 2019, 7:30 AM ]

Our new paper, "Simulations of the regulatory ACT domain of human phenylalanine hydroxylase (PAH) unveil its mechanism of phenylalanine binding" has been chosen as an Editors' Pick by the Journal of Biological Chemistry!  Editors' Picks correspond to the top 2 percent of manuscripts JBC reviews in a year in terms of significance and overall importance. About 50 to 100 papers are selected from the more than 6,600 JBC publishes each year. 

Yunhui Ge, Elias Borne, Shannon Stewart, Michael R. Hansen, Emilia C. Arturo, Eileen K. Jaffe, and Vincent A. Voelz
J. Biol. Chem. 2018 293: 19532. doi:10.1074/jbc.RA118.004909 

See also Yunhui's author profile!

We are doubly excited to learn that that Xuhui Huang et al. have contributed an Editors' Pick Highlight article about our manuscript!

Kirill A. Konovalov, Wei Wang, and Xuhui Huang
J. Biol. Chem. 2018 293: 19544. doi:10.1074/jbc.H118.006676

Voelz Lab welcomes new students Rob and Dylan

posted Jan 3, 2019, 6:44 AM by Vincent Voelz

2019 brings the addition of two new Chemistry Ph.D. students to the Voelz Lab: Robert Raddi and Dylan Novack.  Welcome to the Voelz Lab!

Happy Halloween 2018 from the Voelz Lab

posted Nov 8, 2018, 7:22 AM by Vincent Voelz

Our third annual Halloween-themed group meeting was spooky and scary indeed!  Happy Halloween 2018 from the Voelz group!

Applying BICePs and MSMs to understand the action of a macrolide antibiotic

posted May 24, 2018, 2:13 PM by Vincent Voelz   [ updated May 24, 2018, 7:23 PM ]

In new collaborative work with the Andrade, Leimkuhler Grimes, Dunman and Valentine groups, we have brought our cutting-edge computational methods to bear on the problem of understanding the effects of the macrolide antibiotic albocycline on Staphylococcus aureus, bacteria attributed as a major source of antibiotic resistance.

Based on initial characterizations of albocycline, which suggested a mechanism in which the molecule targets inhibits of peptidoglycan biosynthesis of the bacterial cell wall, our manuscript explores the inhibition of an enzyme called MurA by albocycline.   Experimental studies from the Grimes group showed that albocycline inhibits MurA.  To model the interaction between albocycline MurA, we used our BICePs algorithm to combine QM/REMD modeling and NMR restraints to determine the likely structure of albocycline in solution.   We then performed distributed simulations of the MurA enzyme on Folding@home, generating a large collection of receptor conformations that we could use to homology-model related enzymes and perform computational docking.  Intriguingly, the ensemble-docking studies correctly predicted the relative affinities of albocycline to S. aureus MurA, S. aureus MurZ and E. coli MurA.   However, we also find the albocycline is a more potent antibiotic than can be explained by its affinity for MurA alone, suggesting another target, which may be discovered by future screening of resistance mutants.  

To learn more, check out our full paper in Bioorganic & Medicinal Chemistry:
  • Elucidating the inhibition of peptidoglycan biosynthesis in Staphylococcus aureus by albocycline, a macrolactone isolated from Streptomyces maizeus. Liang, Hai; Zhou, Guangfeng; Ge, Yunhui; D'Ambrosio, Elizabeth; Eidem, Tess; Blanchard, Catlyn; Louka, Cindy; Chatare, Vijay; Dunman, Paul; Valentine, Ann; Voelz, Vincent; Grimes, Catherine; Andrade, Rodrigo, Accepted, Bioorganic & Medicinal Chemistry (2018). doi:10.1016/j.bmc.2018.05.017

Congrats to Yunhui on new BICePs paper

posted Apr 13, 2018, 4:15 PM by Vincent Voelz

Congratulations to Yunhui Ge on the publication of a new first-author manuscript!  In this paper, we explore how to use our BICePs algorithm (Bayesian Inference of Conformational Populations) to objectively compare how consistent various theoretical models are in comparison to sparse experimental data.

To learn more, check out our full paper in the Journal of Physical Chemistry B:
  • Model selection using BICePs: A Bayesian approach to force field validation and parameterization. Yunhui Ge and Vincent A. Voelz, Accepted, Journal of Physical Chemistry B (2018) doi:10.1021/acs.jpcb.7b11871

Voelz Lab at BPS 2018

posted Apr 13, 2018, 3:48 PM by Vincent Voelz   [ updated Apr 13, 2018, 4:05 PM ]

We had a memorable time at the 62nd Annual Meeting of the Biophysical Society, Feb 18–21, 2018 in San Francisco, CA.  

This year Matt Hurley was invited to give a platform talk at BPS and did a great job!  This was his first-ever talk invited to to an international conference.  Yunhui, Hongbin, and Rob gave rousing poster presentation.  See the full list of abstract titles below.
  • Platform Talk: "Enhanced Sampling and Bayesian Inference to Model the Conformational Dynamics of Peptoid Macrocycles". Matthew Hurley, JD Northrup, Vincent Voelz, Chris Schafmeister
  • Poster: "Reconciling Simulated Ensembles of Apomyoglobin with Experimental HDX Data". Hongbin Wan, Yunhui Ge, Asghar Razavi, Vincent Voelz
  • Poster: "Binding Pathways of Phenylalanine to the Dimeric Regulatory Domain of Human PAH Reveal a Lid Gating Mechanism". Yunhui Ge, Eileen K. Jaffe, Vincent A. Voelz.
  • Poster: "A Markov State Model of Solvent Features Reveals The  Role of Water in Protein-Protein Binding". Robert M. Raddi, and Vincent A. Voelz
Some pics:

Congrats to Guangfeng on a successful PhD defense!

posted Nov 3, 2017, 5:37 PM by Vincent Voelz

Dr. Guangfeng Zhou has successfully defended his thesis work, earning himself a Ph.D. in Chemistry.  After submitting his dissertation "Statistical models and their applications in studying biomolecular conformational dynamics", Guangfeng is off to postdoctoral work with Frank DiMaio at the Institute for Protein Design at the University of Washington in Seattle.  Congrats Guangfeng!

Happy Halloween from the Voelz Lab

posted Nov 3, 2017, 5:22 PM by Vincent Voelz

With our second annual Halloween-themed group meeting behind us, it appears we have started a new spook-tacular tradition.   Happy Halloween 2017 from the Voelz group!

New paper on peptoid-porphyrin conjugates

posted Oct 31, 2017, 3:36 PM by Vincent Voelz

Our collaborative work with the Jiwon Seo group has just been published!  The new manuscript, "Control of porphyrin interactions via structural change of peptoid scaffold", describes a helical peptoid scaffold that can be functionalized by conjugating porphyrin groups at specific positions.  Using a combination of experiment and molecular modeling, we show that a more rigid peptoid-porphyrin linker results in improved conformational properties.   These studies move a step closer to designing foldameric molecules that can mimic the light-harvesting photosynthetic complexes found in nature. 

Woojin Yang, Boyeong Kang, Vincent A. Voelz, Jiwon Seo, Org. Biomol. Chem. (2017) doi:10.1039/C7OB02398G

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