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

Sara wins Honorable Mention at the URP Research Symposium

posted Oct 10, 2017, 9:19 AM by Vincent Voelz

Congratulations to Sara Dornblaser, whose poster won Honorable Mention at Undergraduate Research Program (URP) Fall Research Symposium.  Her presentation, entitled "Molecular simulations reveal the importance of disulfide bridging in PrgW, a putative redox switch for plasmid replication", is a collaboration between the Voelz Lab and Bettina Buttaro's group in the Department of Microbiology and Immunology at Temple School of Medicine.


New BiophysJ paper on p53-MDM2 binding

posted Aug 22, 2017, 9:21 AM by Vincent Voelz   [ updated Aug 22, 2017, 9:24 AM ]

Congrats to Guangfeng Zhou on his first-author paper just published in Biophysical Journal!  This work is currently featured on the front webpage of the Aug. 22 issue.

In this work, we analyzed over 800 µs of explicit-solvent  ab initio binding simulations of the p53 TAD peptide to MDM2, to obtain a detailed picture of the binding mechanism.  Kinetic network models built from the trajectory data reveal a binding-then-folding mechanism, which we further connect to macroscopic binding flux models, enabling physiological insight into the binding of intrinsically disordered peptides (IDPs) like p53 TAD.

New JCIM paper on Designed Beta-Cap Hairpins

posted Aug 18, 2017, 7:24 PM by Vincent Voelz   [ updated Aug 18, 2017, 7:25 PM ]

Congratulations to Yunhui on his first-author paper!  In this work, a collaboration with the Andersen lab at UW, we compare simulation predictions against experimental NMR and CD data for a series of designed beta-hairpins stabilized by a Trp-Trp capping motifs.  You can read the full paper here

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