CV, Publications and recent Talks
CV
2006+ University of California San Diego (UCSD), Center for Theoretical Biological Physics (CTBP) Postdoctoral scholar in the research group of
Prof. J. Onuchic2005 University of Kobe Postdoctoral scholar in the research group of Prof. S. Tanaka 2002-2005 University of Dortmund and
Research Center Karlsruhe, Institute of NanotechnologyDoctorate in Physics, thesis on "Free Energy Simulations using Stochastic Optimization Methods for Protein Structure Prediction", thesis advisor Priv.-Doz. W. Wenzel 1996-2001 University of Dortmund Student of Physics, 2001 Diploma in Physics 1986-1995 St. Josef Gymnasium Bocholt Secondary school, university entrance diploma ("Abitur") with majors in Physics and Mathematics
Awards and Fellowships
2006 German Chemical Society (GdCH), FIZ Chemie Award for best PhD-thesis in 2005 2005 University of Dortmund, Faculty of Physics Award for best PhD thesis in 2005 2004 Symposium for theoretical Chemistry Award for outstanding poster presentation (5 out of 133 contributions awarded) 1999-2001 Konrad Adenauer Stiftung Scholarship for my studies
Extracurricular Activities
2002-2005 AEGEE- Karlsruhe President in term 2003/2004, delegate for international statute meetings, organisation of international events 1996-2001 University of Dortmund, Faculty of Physics Student representative in faculty meetings, member of several commitess including various search commitess for new professors/faculty positions and reformation of studies 1996-2001 University of Dortmund, Fachschaft Physik Member of students council, President in term 1997/1998 Publications
Schug, A. , Weigt, M., Hoch, J.A., Onuchic, J.N., Hwa, T., & Szurmant, H. (2010), "Computational modeling of phosphotransfer complexes in two-component signaling", Meth. Enzymol. BibTeX: @article{Schug2010, author = {A. Schug and M. Weigt and J.A. Hoch and J.N. Onuchic and T. Hwa and H. Szurmant}, title = {Computational modeling of phosphotransfer complexes in two-component signaling}, journal = {Meth Enzymol}, year = {2010}, volume = {in press}, pages = {} }Schug, A., Weigt, M., Onuchic, J.N., Hwa, T., & Szurmant, H. (2009), "High resolution protein complexes from integrating genomic information with molecular simulation", Proc. Nat. Acad. Sci. U.S.A. BibTeX: @article{Schug2009, author = {A. Schug and M. Weigt and J.N. Onuchic and T. Hwa and H. Szurmant}, title = {High resolution protein complexes from integrating genomic information with molecular simulation}, journal = {Proc Natl Acad Sci U S A}, year = {2009}, volume = {106}, pages = {22124-22129} }Lammert, H., Schug, A. & Onuchic, J. (2009), "Robustness and generalization of structure-based models for protein folding and function", Proteins: Structure, Function and Bioinformatics. BibTeX: @article{Lammert2009, author = {H. Lammert and A. Schug and J.N. Onuchic}, title = {Robustness and generalization of structure-based models for protein folding and function}, journal = {Proteins: Structure, Function and Bioinformatics (in press)}, year = {2009}, volume = {77}, pages = {881-891} }Gambin*, Y., Schug*, A., Lemke, E.A., Lavinder, J.J., Ferreon, A.C.M., Magliery, T.J., Onuchic, J.N. & Deniz, A.A. (* indicated equal contribution), (2009), "Direct single-molecule observation of a protein living in two opposed native structures", Proc Natl Acad Sci U S A. BibTeX: @article{Gambin*2009, author = {Yann Gambin and Alexander Schug and Edward A. Lemke and Jason J. Lavinder and Allan Chris M. Ferreon and Thomas J. Magliery and Jose' N. Onuchic and Ashok A. Deniz}, title = {Direct single-molecule observation of a protein living in two opposed native structures}, journal = {Proc Natl Acad Sci U S A}, year = {2009}, volume = {106}, pages = {10153-10158} }Whitford, P.C., Schug, A., Saunders, J., Hennelly, S.P., Onuchic, J.N. & Sanbonmatsu, K.Y. (2009), "Nonlocal helix formation is key to understanding S-adenosylmethionine-1 riboswitch function.", Biophys J., Jan, 2009. Vol. 96(2), pp. L7-L9. Abstract: Riboswitches are noncoding RNAs that regulate gene expression in response to changing concentrations of specific metabolites. Switching activity is affected by the interplay between the aptamer domain and expression platform of the riboswitch. The aptamer domain binds the metabolite, locking the riboswitch in a ligand-bound conformation. In absence of the metabolite, the expression platform forms an alternative secondary structure by sequestering the 3' end of a nonlocal helix called P1. We use all-atom structure-based simulations to characterize the folding, unfolding, and metabolite binding of the aptamer domain of the S-adenosylmethionine-1 (SAM-1) riboswitch. Our results suggest that folding of the nonlocal helix (P1) is rate-limiting in aptamer domain formation. Interestingly, SAM assists folding of the P1 helix by reducing the associated free energy barrier. Because the 3' end of the P1 helix is sequestered by an alternative helix in the absence of metabolites, this observed ligand-control of P1 formation provides a mechanistic explanation of expression platform regulation. BibTeX: @article{Whitford2009a, author = {Paul C Whitford and Alexander Schug and John Saunders and Scott P Hennelly and Jose N Onuchic and Kevin Y Sanbonmatsu}, title = {Nonlocal helix formation is key to understanding S-adenosylmethionine-1 riboswitch function.}, journal = {Biophys J}, year = {2009}, volume = {96}, number = {2}, pages = {L7--L9}, url = {http://dx.doi.org/10.1016/j.bpj.2008.10.033}, doi = {http://dx.doi.org/10.1016/j.bpj.2008.10.033} }Whitford, P.C., Noel, J.K., Gosavi, S., Schug, A., Sanbonmatsu, K.Y. & Onuchic, J.N. (2009), "An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields.", Proteins., May, 2009. Vol. 75(2), pp. 430-441. Abstract: Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase, and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a C(alpha) structure-based model and an all-atom empirical forcefield. Key findings include: (1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature, (2) folding mechanisms are robust to variations of the energetic parameters, (3) protein folding free-energy barriers can be manipulated through parametric modifications, (4) the global folding mechanisms in a C(alpha) model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model, and (5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Because this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function. BibTeX: @article{Whitford2009b, author = {Paul C Whitford and Jeffrey K Noel and Shachi Gosavi and Alexander Schug and Kevin Y Sanbonmatsu and Jose N Onuchic}, title = {An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields.}, journal = {Proteins}, year = {2009}, volume = {75}, number = {2}, pages = {430--441}, url = {http://dx.doi.org/10.1002/prot.22253}, doi = {http://dx.doi.org/10.1002/prot.22253} }Oliveira, L.C., Schug, A. & Onuchic, J.N. (2008), "Geometrical features of the protein folding mechanism are a robust property of the energy landscape: A detailed investigation of several reduced models", Journal Of Physical Chemistry B. Vol. 112(19), pp. 6131-6136. Abstract: The concept of a funneled energy landscape and the principle of minimal frustration are the theoretical foundation justifying the applicability of structure-based models. In simulations, a protein is commonly reduced to a C-alpha-bead representation. These simulations are sufficient to predict the geometrical features of the folding mechanism observed experimentally utilizing a concise formulation of the Hamiltonian with low computational costs. Toward a better understanding of the interplay between energetic and geometrical features in folding, the side chain is now explicitly included in the simulations. The simplest choice is the addition of C-beta-beads at the center-of-mass position of the side chains. While one varies the energetic parameters of the model, the geometric aspects of the folding mechanism remain robust for a broad range of parameters. Energetic properties like folding barriers and protein stability are sensitive to the details of simulations. This robustness to geometry and sensitivity to energetic properties provide flexibility in choosing different parameters to represent changes in sequences, environments, stability or folding rate effects. Therefore, minimal frustration and the funnel concept guarantee that the geometrical features are robust properties of the folding landscape, while mutations and/or changes in the environment easily influence energy-dependent properties like folding rates or stability. BibTeX: @article{Oliveira2008a, author = {Oliveira, L. C. and Schug, A. and Onuchic, J. N.}, title = {Geometrical features of the protein folding mechanism are a robust property of the energy landscape: A detailed investigation of several reduced models}, journal = {Journal Of Physical Chemistry B}, year = {2008}, volume = {112}, number = {19}, pages = {6131--6136} }Schug, A., Whitford, P.C., Levy, Y. & Onuchic, J.N. (2007), "Mutations as trapdoors to two competing native conformations of the Rop-dimer", Proceedings Of The National Academy Of Sciences Of The United States Of America. Vol. 104, pp. 17674-17679. Abstract: Conformational transitions play a central role in regulating protein function. Structure-based models with multiple basins have been used to understand the mechanisms governing these transitions. A model able to accommodate multiple folding basins is proposed to explore the mutational effects in the folding of the Rop-dimer (Rop). In experiments, Rop mutants show unusually strong increases in folding rates with marginal effects on stability. We investigate the possibility of two competing conformations representing a parallel (P) and the wild-type antiparallel (AP) arrangement of the monomers as possible native conformations. We observe occupation of both distinct states and characterize the transition pathways. An interesting observation from the simulations is that, for equivalent energetic bias, the transition to the P basin (non-wild-type basin) shows a lower free-energy barrier. Thus, the rapid kinetics observed in experiments appear to be the result of two competing states with different kinetic behavior, triggered upon mutation by the opening of a trapdoor arising from Rop's symmetric structure. The general concept of having competing conformations for the native state goes beyond explaining Rop's mutational behaviors and can be applied to other systems. A switch between competing native structures might be triggered by external factors to allow, for example, allosteric control or signaling. BibTeX: @article{Schug2007b, author = {Schug, A. and Whitford, P. C. and Levy, Y. and Onuchic, J. N.}, title = {Mutations as trapdoors to two competing native conformations of the Rop-dimer}, journal = {Proceedings Of The National Academy Of Sciences Of The United States Of America}, year = {2007}, volume = {104}, pages = {17674--17679} }Maeda, K., Schug, A., Watanabe, H., Fukuzawa, K., Mochizuki, Y., Nakano, T. & Tanaka, S. (2007), "Effects of Point Mutations on the Binding Energies of Estrogen Receptor with Estradiol", J. Comput. Chem. Jpn.. Vol. 6, pp. 33-46. BibTeX: @article{Maeda2007, author = {K. Maeda and A. Schug and H. Watanabe and K. Fukuzawa and Y. Mochizuki and T. Nakano and S. Tanaka}, title = {Effects of Point Mutations on the Binding Energies of Estrogen Receptor with Estradiol}, journal = {J. Comput. Chem. Jpn.}, year = {2007}, volume = {6}, pages = {33-46} }Verma, A., Schug, A., Lee, K.H. & Wenzel, W. (2006), "Basin Hopping Simulations for All-Atom Protein Folding", J. Chem. Phys.. Vol. 124, pp. 044515. BibTeX: @article{Verma2006, author = {A. Verma and A. Schug and K. H. Lee and W. Wenzel}, title = {Basin Hopping Simulations for All-Atom Protein Folding}, journal = {J. Chem. Phys.}, year = {2006}, volume = {124}, pages = {044515} }Schug, A. & Wenzel, W. (2006), "An evolutionary strategy for all-atom protein folding of the sixty-amino acid bacterial ribosomal protein L20", Biophys. J.. Vol. 90, pp. 4273-4280. BibTeX: @article{Schug2006a, author = {A. Schug and W. Wenzel}, title = {An evolutionary strategy for all-atom protein folding of the sixty-amino acid bacterial ribosomal protein L20}, journal = {Biophys. J.}, year = {2006}, volume = {90}, pages = {4273-4280} }Schug, A., Wenzel, W. & Hansmann, U. (2005), "Energy Landscape Paving Simulations of the trp-cage Protein", J. Chem. Phys.. Vol. 122, pp. 194711. BibTeX: @article{Schug2005h, author = {A. Schug and W. Wenzel and U.H.E. Hansmann}, title = {Energy Landscape Paving Simulations of the trp-cage Protein}, journal = {J. Chem. Phys.}, year = {2005}, volume = {122}, pages = {194711} }Schug, A., Verma, A., Herges, T., Lee, K. & Wenzel, W. (2005), "Comparison of Stochastic Optimization Methods for All-Atom Folding of the Trp-Cage Protein", ChemPhysChem. Vol. 6(12), pp. 2640-2646. BibTeX: @article{Schug2005d, author = {A. Schug and A. Verma and T. Herges and K.H. Lee and W. Wenzel}, title = {Comparison of Stochastic Optimization Methods for All-Atom Folding of the Trp-Cage Protein}, journal = {ChemPhysChem}, year = {2005}, volume = {6}, number = {12}, pages = {2640-2646} }Schug, A., Herges, T., Verma, A. & Wenzel, W. (2005), "Investigation of the parallel tempering method for protein folding", Phys. Cond. Matter, special issue: Structure and Function of Biomolecules. Vol. 17, pp. 1641-1650. BibTeX: @article{Schug2005b, author = {A. Schug and T. Herges and A. Verma and W. Wenzel}, title = {Investigation of the parallel tempering method for protein folding}, journal = {Phys. Cond. Matter, special issue: Structure and Function of Biomolecules}, year = {2005}, volume = {17}, pages = {1641-1650} }Schug, A., Fischer, B., Verma, A., Merlitz, H., Wenzel, W. & Schoen, G. (2005), "Biomolecular structure prediction with stochastic optimization methods", Adv. Eng. Materials. Vol. 11, pp. 1005-1009. BibTeX: @article{Schug2005a, author = {A. Schug and B. Fischer and A. Verma and H. Merlitz and W. Wenzel and G. Schoen}, title = {Biomolecular structure prediction with stochastic optimization methods}, journal = {Adv. Eng. Materials}, year = {2005}, volume = {11}, pages = {1005-1009} }Schug, A. & Wenzel, W. (2004), "All-atom folding of the trp-cage protein with an adaptive parallel tempering method", Europ. Phys. Lett.. Vol. 67, pp. 307-313. BibTeX: @article{Schug2004c, author = {A. Schug and W. Wenzel}, title = {All-atom folding of the trp-cage protein with an adaptive parallel tempering method}, journal = {Europ. Phys. Lett.}, year = {2004}, volume = {67}, pages = {307-313} }Schug, A., Herges, T. & Wenzel, W. (2004), "All atom folding of the three helix HIV accessory protein with an adaptive parallel tempering method", Proteins: Structure, Function, and Bioinformatics. Vol. 57(4), pp. 792-798. BibTeX: @article{Schug2004a, author = {A. Schug and T. Herges and W. Wenzel}, title = {All atom folding of the three helix HIV accessory protein with an adaptive parallel tempering method}, journal = {Proteins: Structure, Function, and Bioinformatics}, year = {2004}, volume = {57}, number = {4}, pages = {792-798} }Schug, A., Herges, T. & Wenzel, W. (2004), "Reproducible folding of a four helix protein in an all-atom forcefield", J. Am. Chem. Soc.. Vol. 126(51), pp. 16736-16737. BibTeX: @article{Schug2004b, author = {A. Schug and T. Herges and W. Wenzel}, title = {Reproducible folding of a four helix protein in an all-atom forcefield}, journal = {J. Am. Chem. Soc.}, year = {2004}, volume = {126}, number = {51}, pages = {16736-16737} }Schug, A., Herges, T. & Wenzel, W. (2003), "Reproducible Protein Folding with the Stochastic Tunneling Method", Phys. Rev. Letters., October, 2003. Vol. 91(15), pp. 158102. BibTeX: @article{Schug2003, author = {A. Schug and T. Herges and W. Wenzel}, title = {Reproducible Protein Folding with the Stochastic Tunneling Method}, journal = {Phys. Rev. Letters}, year = {2003}, volume = {91}, number = {15}, pages = {158102} }Herges, T., Schug, A., Burghardt, B., Merlitz, H. & Wenzel, W. (2003), "Stochastic Optimization Methods for Structure Prediction of Biomolecular Nanoscale Systems", Nanotechnology. Vol. 14, pp. 1161-1167. BibTeX: @article{Herges2003, author = {T. Herges and A. Schug and B. Burghardt and H. Merlitz and W. Wenzel}, title = {Stochastic Optimization Methods for Structure Prediction of Biomolecular Nanoscale Systems}, journal = {Nanotechnology}, year = {2003}, volume = {14}, pages = {1161-1167} }
Bookchapters
Schug*, A., Hyeon*, C., Onuchic, J.N. & (* indicates euqal contribution), (2009), "Coarse-grained structure-based simulations on Proteins and RNA" G.A. Voth. BibTeX: @book{Schug*2009, author = {A. Schug* and C. Hyeon* and J. N. Onuchic and (* indicates equal contribution)}, title = {Coarse-grained structure-based simulations on Proteins and RNA}, publisher = {G.A. Voth}, pages = {123-140}, year = {2009} }A. Verma, S.M. Gopal, A. Schug, T. Herges, K. Klenin and W. Wenzel. (2008), "All-atom Protein Folding with Free-Energy Forcefields" BibTeX: @book{Verma2008, author = {A. Verma and S.M. Gopal and A. Schug and T. Herges and K. Klenin and W. Wenzel.}, title = {All Atom Protein Folding with Free-Energy Forcefields}, journal = {Molecular Biology of Protein Folding Pt. A}, number ={81}, pages = {181-253}, year = {2008} }Schug, A., Verma, A., Lee, K. & Wenzel, W. (2005), "All Atom Protein Structure Prediction with Stochastic Optimization Methods" Vol. Modern Methods for Theoretical Physical Chemistry of Biopolymers, pp. 319-330. Elsevier. BibTeX: @book{Schug2005o, author = {A. Schug and A. Verma and K.H. Lee and W. Wenzel}, title = {All Atom Protein Structure Prediction with Stochastic Optimization Methods}, publisher = {Elsevier}, year = {2005}, volume = {Modern Methods for Theoretical Physical Chemistry of Biopolymers}, pages = {319-330} }
Conference Proceedings and other publications
Schug, A., Gambin, Y., Ashok., A.A. & Onuchic, J. (2009), "The Rop-Dimer: A Folded Protein Living Between Two Alternate Structures", Biophys. J., Vol. 96, 568a-568a. BibTeX: @conference{Schug2009bj, author = {A. Schug and Y. Gambin and A. A. Deniz and J. N. Onuchic}, title = {The Rop-Dimer: A Folded Protein Living Between Two Alternate Structures}, booktitle = {Biophysical Journal}, year = {2009}, volume = {96}, pages = {568a-568a} }Schug, A. & Onuchic, J. (2008), "Mutations as Trapdoors: The Rop-dimer with Two Competing Native Conformations", Publication Series of the John von Neumann Institute for Computing. Vol. 40, pp. 137-140. BibTeX: @conference{Schug2008, author = {A. Schug and J. Onuchic}, title = {Mutations as Trapdoors: The Rop-dimer with Two Competing Native Conformations}, booktitle = {Publication series of the John von Neumann Instite for Computing}, year = {2008}, volume = {40}, pages = {137-140} }Verma, A., Gopan, S.M., Schug, A., Oh, J.S., Kleinin K., Lee, K.H. & Wenzel, W. (2007), "Massively parallel all-atom protein folding in a single day", Publication Series of the John von Neumann Institute for Computing. Vol. 38, pp. 527-534. BibTeX: @conference{verma2007, author = {A. Verma and S.M. Gopal and A. Schug and J.S. Oh and K. Klenin and K.H. Lee and W. Wenzel}, title = {Massively parallel all-atom protein folding in a single day}, booktitle = {Publication series of the John von Neumann Instite for Computing}, year = {2007}, volume = {38}, pages = {527-534} }Schug, A. & Onuchic, J. (2007), "Symmetric mutations and their asymmetric effect on a dual-funneled energy landscape: Modelling the Rop-dimer", Biophysical Journal. , pp. 216A-216A. BibTeX: @conference{Schug2007c, author = {Schug, A. and Onuchic, J.}, title = {Symmetric mutations and their asymmetric effect on a dual-funneled energy landscape: Modelling the Rop-dimer}, journal = {Biophysical Journal}, year = {2007}, pages = {216A--216A} }Schug, A., Verma, A., Lee, K.H. & Wenzel, W. (2005), "Stochastic Optimization Methods for Protein Folding", Proceedings of the WSEAS Conference on Simulation, Modeling and Optimization. WSEAS. BibTeX: @conference{Schug2005g, author = {A. Schug and A. Verma and K. H. Lee and W. Wenzel}, title = {Stochastic Optimization Methods for Protein Folding}, journal = {Proceedings of the WSEAS Conference on Simulation, Modeling and Optimization. WSEAS}, year = {2005} }Schug, A., Verma, A., Lee, K. & Wenzel, W. (2005), "All atom protein folding: A progress report", WSEAS Transactions. Vol. 2, pp. 1955-1964. BibTeX: @conference{Schug2005f, author = {A. Schug and A. Verma and K.H. Lee and W. Wenzel}, title = {All atom protein folding: A progress report}, journal = {WSEAS Transactions}, year = {2005}, volume = {2}, pages = {1955-1964} }Schug, A., Herges, T. & Wenzel, W. (2005), "All atom protein folding with stochastic optimization methods", Biophys. J.. Vol. 88, pp. 332A-332A. BibTeX: @conference{Schug2005c, author = {A. Schug and T. Herges and W. Wenzel}, title = {All atom protein folding with stochastic optimization methods}, journal = {Biophys. J.}, year = {2005}, volume = {88}, pages = {332A-332A} }Herges, T., Schug, A. & Wenzel, W. (2003), "Low Energy Conformations of a three Helix Peptide in an all Atom Forcefield", Nanotech., In Technical Proceedings of the 2003 Nanotechnology Conference and Trade Show. Vol. 1, pp. 90-93. BibTeX: @conference{Herges2003a, author = {T. Herges and A. Schug and W. Wenzel}, title = {Low Energy Conformations of a three Helix Peptide in an all Atom Forcefield}, booktitle = {Technical Proceedings of the 2003 Nanotechnology Conference and Trade Show}, journal = {Nanotech}, year = {2003}, volume = {1}, pages = {90-93} }Schug, A. & Onuchic, J.N. (), "Competition between native conformations of proteins: the Rop-dimer", http://ctbp.ucsd.edu/nuggets/schug_nugget_08.pdf. BibTeX: @misc{Schug, author = {A. Schug and J. N. Onuchic}, title = {Competition between native conformations of proteins: the Rop-dimer}, howpublished = {http://ctbp.ucsd.edu/nuggets/schug_nugget_08.pdf} }Schug, A. (2005), "Free-Energy Simulations using Stochastic Optimization Methods for Protein Structure Prediction", PhD Thesis. BibTeX: @phdthesis{Schug2005, author = {A. Schug}, title = {Free-Energy Simulations using Stochastic Optimization Methods for Protein Structure Prediction}, journal = {PhD Thesis}, year = {2005} }Recent Talks
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