Adrian H. Elcock, PhD

Portrait
Professor of Biochemistry

Contact Information

Primary Office
4-530 BSB
Iowa City, IA 52242
319-335-6643

Education

BSc, Department of Chemistry, University of East Anglia
DrPH, Department of Chemistry, Oxford University
Fellow, Department of Chemistry and Biochemistry, University of California, San Diego

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Research Summary

Work in my laboratory focuses on using molecular simulation techniques to address a variety of fundamental biophysical questions. Research areas in which we have recently published work include: (1) simulation of diffusion and association of proteins in highly concentrated solutions (such as those that are found inside living cells), (2) simulation of amino acid associations at the very high temperatures encountered by hyperthermophilic organisms, (3) computational prediction of drug-receptor interactions, with a view to identifying all cellular targets of current anti-cancer drugs, and (4) computational prediction of functionally important residues in proteins given only the protein's structure. Other research areas that we have recently developed interests in include: (1) computational identification of cryptic binding sites in proteins that might be used to develop novel inhibitors, (2) molecular simulations of protein folding in physiological conditions (including the effects of chaperonins), (3) modeling the role of conformational flexibility in protein-protein association events, and (4) experimentally measuring the affinities of drug-receptor interactions to provide reliable data for testing our computational methods. Students in my laboratory come from a wide range of backgrounds, and do not have to be experts in the use of computers: most of our work involves developing ideas in our heads, and computer simulations are typically only used to test these ideas. To complement our simulation work, we will in the near future also be increasingly conducting our own experiments: students joining my laboratory will therefore have the opportunity to undertake combined theoretical and experimental research projects.

Publications

Hacker, W. C., Li, S. & Elcock, A. H. (2017). Features of genomic organization in a nucleotide-resolution molecular model of the Escherichia coli chromosome. Nucleic acids research, 45(13), 7541-7554. PMID: 28645155.

Lay, W. K., Miller, M. S. & Elcock, A. H. (2017). Reparameterization of Solute-Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations. Journal of chemical theory and computation, 13(5), 1874-1882. PMID: 28437100.

Andrews, C. T., Campbell, B. A. & Elcock, A. H. (2017). Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations. Journal of chemical theory and computation, 13(4), 1794-1811. PMID: 28288277.

Miller, M. S., Lay, W. K., Li, S., Hacker, W. C., An, J., Ren, J. & Elcock, A. H. (2017). Reparametrization of Protein Force Field Nonbonded Interactions Guided by Osmotic Coefficient Measurements from Molecular Dynamics Simulations. Journal of chemical theory and computation, 13(4), 1812-1826. PMID: 28296391.

Miller, M. S., Lay, W. K. & Elcock, A. H. (2016). Osmotic Pressure Simulations of Amino Acids and Peptides Highlight Potential Routes to Protein Force Field Parameterization. The journal of physical chemistry. B, 120(33), 8217-29. PMID: 27052117.

Chen, R., Subramanyam, S., Elcock, A. H., Spies, M. & Wold, M. S. (2016). Dynamic binding of replication protein a is required for DNA repair. Nucleic acids research, 44(12), 5758-72. PMID: 27131385.

Clark, P. L., Elcock, A. H. (2016). Molecular chaperones: providing a safe place to weather a midlife protein-folding crisis. Nature structural & molecular biology, 23(7), 621-3. PMID: 27384188.

Lay, W. K., Miller, M. S. & Elcock, A. H. (2016). Optimizing Solute-Solute Interactions in the GLYCAM06 and CHARMM36 Carbohydrate Force Fields Using Osmotic Pressure Measurements. Journal of chemical theory and computation, 12(4), 1401-7. PMID: 26967542.

Schrodt, M. V., Andrews, C. T. & Elcock, A. H. (2015). Large-Scale Analysis of 48 DNA and 48 RNA Tetranucleotides Studied by 1 ┬Ás Explicit-Solvent Molecular Dynamics Simulations. Journal of chemical theory and computation, 11(12), 5906-17. PMID: 26580891.

Cressiot, B., Braselmann, E., Oukhaled, A., Elcock, A. H., Pelta, J. & Clark, P. L. (2015). Dynamics and Energy Contributions for Transport of Unfolded Pertactin through a Protein Nanopore. ACS nano, 9(9), 9050-61. PMID: 26302243.

Li, S., Elcock, A. H. (2015). Residue-Specific Force Field (RSFF2) Improves the Modeling of Conformational Behavior of Peptides and Proteins. The journal of physical chemistry letters, 6(11), 2127-33. PMID: 26266514.

Frembgen-Kesner, T., Andrews, C. T., Li, S., Ngo, N. A., Shubert, S. A., Jain, A., Olayiwola, O. J., Weishaar, M. R. & Elcock, A. H. (2015). Parametrization of Backbone Flexibility in a Coarse-Grained Force Field for Proteins (COFFDROP) Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of All Possible Two-Residue Peptides. Journal of chemical theory and computation, 11(5), 2341-54. PMID: 26574429.

Brown, R. F., Andrews, C. T. & Elcock, A. H. (2015). Stacking Free Energies of All DNA and RNA Nucleoside Pairs and Dinucleoside-Monophosphates Computed Using Recently Revised AMBER Parameters and Compared with Experiment. Journal of chemical theory and computation, 11(5), 2315-28. PMID: 26574427.

Li, S., Andrews, C. T., Frembgen-Kesner, T., Miller, M. S., Siemonsma, S. L., Collingsworth, T. D., Rockafellow, I. T., Ngo, N. A., Campbell, B. A., Brown, R. F., Guo, C., Schrodt, M., Liu, Y. T. & Elcock, A. H. (2015). Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field. Journal of chemical theory and computation, 11(3), 1315-29. PMID: 26579777.

Andrews, C., Elcock, A. (2014). COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids. J Chem Theory Comput, 10(11), 5178-5194. PMID: 25400526.

Azzaz, A., Vitalini, M., Thomas, A., Price, J., Blacketer, M., Cryderman, D., Zirbel, L., Woodcock, C., Elcock, A., Wallrath, L. & Shogren-Knaak, M. (2014). Human heterochromatin protein 1a promotes nucleosome associations that drive chromatin condensation. J Biol Chem, 289(10), 6850-61. PMID: 24415761.

Theillet, F., Binolfi, A., Frembgen-Kesner, T., Hingorani, K., Sarkar, M., Kyne, C., Li, C., Crowley, P., Gierasch, L., Pielak, G., Elcock, A., Gershenson, A. & Selenko, P. (2014). Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs). Chem Rev, 114(13), 6661-714. PMID: 24901537.

Randak, C. O., Dong, Q., Ver Heul, A. R., Elcock, A. H. & Welsh, M. J. (2013). ATP and AMP mutually influence their interaction with the ATP-binding cassette (ABC) adenylate kinase cystic fibrosis transmembrane conductance regulator (CFTR) at separate binding sites. J Biol Chem, 288(38), 27691-701. PMID: 23921386.

Stark, A. C., Andrews, C. T. & Elcock, A. H. (2013). Toward optimized potential functions for protein-protein interactions in aqueous solutions: osmotic second virial coefficient calculations using the MARTINI coarse-grained force field. J Chem Theory Comput., 9(9). PMID: 24223529.

Thomas, A. S., Mao,, S. & Elcock, A. H. (2013). Flexibility of the bacterial chaperone trigger factor in microsecond-timescale molecular dynamics simulations. Biophys J, 105(3), 732-744. PMID: 23931321.

Elcock, A. H. (2013). A molecule-centered method for accelerating the calculation of hydrodynamic interactions in Brownian dynamics simulations containing many flexible biomolecules. J Chem Theory Comput, 9(7), 3224-3239. PMID: 23914146.

Zhu,, S., Travis,, S. M. & Elcock, A. H. (2013). Accurate calculation of mutational effects on the thermodynamics of inhibitor binding to p38aMAP kinase: a combined computational and experimental study. J Chem Theory Comput, 9(7), 3151-3164. PMID: 23914145.

Frembgen-Kesner, T., Elcock, A. H. (2013). Computer simulations of the bacterial cytoplasm. Biophys Rev, 5(2), 109-119. PMID: 23914257.

Andrews, C. T., Elcock, A. H. (2013). Molecular Dynamics Simulations of Highly Crowded Amino Acid Solutions: Comparisons of Eight Different Force Field Combinations with Experiment and with Each Other. J. Chem. Theory Comput, 9(10), 4585-4602. PMID: 24409104.

Reinert, Z. E., Musselman, E. D., Elcock, A. H. & Horne, W. S. (2012). A PEG-based oligomer as a backbone replacement for surface-exposed loops in a protein tertiary structure. Chembiochem : a European journal of chemical biology, 13(8), 1107-11. PMID: 22539233.

Thomas, A. S., Elcock, A. H. (2011). Direct measurement of the kinetics and thermodynamics of association of hydrophobic molecules from molecular dynamcis simulations.

Thomas, A. S., Elcock, A. H. (2011). Molecular dynamics simulations predict a favorable and unique mode of interaction between lithium (Li+) ions and hydrophobic molecules in aqueous solution.

Frembgen-Kesner, T., Elcock, A. H. (2010). Absolute protein-protein association rate constants from flexible, coarse-grained Brownian dynamics simulations: the role of intermolecular hydrodynamic interactions in barnase-barstar association. Biophysical journal, 99(9), L75-7. PMID: 21044566.

Frembgen-Kesner, T., Elcock, A. H. (2010). Absolute protein-protein association rate contants from flexible, coarse-grained Brownian dynamics simulations: the role of intermolecular hydrodynamic interactions in barnase-barstar association. PMID: 21044566.

Elcock, A. H. (2010). Models of macromolecular crowding effects and the need for quantitative comparisons with experiment. Current opinion in structural biology, 20(2), 196-206. PMID: 20167475.

McGuffee, S. R., Elcock, A. H. (2010). Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm. PLoS computational biology, 6(3), e1000694. PMID: 20221255.

Zhu, S., Elcock, A. H. (2010). A Complete Thermodynamic Characterization of Electrostatic and Hydrophobic Associations in the Temperature Range 0 to 100 degrees C from Explicit-Solvent Molecular Dynamics Simulations. (Vols. 6). (4), pp. 1293-1306. Journal of Chemical Theory and Computation.

Frembgen-Kesner, T., Elcock, A. H. (2009). Striking effects of hydrodynamic interactions on the simulated diffusion and folding of proteins.

Brandt, F., Etchells, S. A., Ortiz, J. O., Elcock, A. H., Hartl, F. U. & Baumeister, W. (2009). The native 3D organization of bacterial polysomes. Cell, 136(2), 261-71. PMID: 19167328.

Thomas, A. S., Elcock, A. H. (2007). Molecular dynamics simulations of hydrophobic associations in aqueous salt solutions indicate a connection between water hydrogen bonding and the Hofmeister effect. Journal of the American Chemical Society, 129(48), 14887-98. PMID: 17994735.

Rockey, W. M., Elcock, A. H. (2006). Structure selection for protein kinase docking and virtual screening: homology models or crystal structures?. Current protein & peptide science, 7(5), 437-57. PMID: 17073695.

McGuffee, S. R., Elcock, A. H. (2006). Atomically detailed simulations of concentrated protein solutions: the effects of salt, pH, point mutations, and protein concentration in simulations of 1000-molecule systems. Journal of the American Chemical Society, 128(37), 12098-110. PMID: 16967959.

Elcock, A. H. (2006). Molecular simulations of cotranslational protein folding: fragment stabilities, folding cooperativity, and trapping in the ribosome. PLoS computational biology, 2(7), e98. PMID: 16789821.

Thomas, A. S., Elcock, A. H. (2006). Direct observation of salt effects on molecular interactions through explicit-solvent molecular dynamics simulations: differential effects on electrostatic and hydrophobic interactions and comparisons to Poisson-Boltzmann theory. Journal of the American Chemical Society, 128(24), 7796-806. PMID: 16771493.

Frembgen-Kesner, T., Elcock, A. H. (2006). Computational sampling of a cryptic drug binding site in a protein receptor: explicit solvent molecular dynamics and inhibitor docking to p38 MAP kinase. Journal of molecular biology, 359(1), 202-14. PMID: 16616932.

Rockey, W. M., Elcock, A. H. (2006). Rapid computational identification of the targets of protein kinase inhibitors. Current opinion in drug discovery & development, 9(3), 326-31. PMID: 16729728.

Rockey, W. M., Elcock, A. H. (2005). Rapid computational identification of the targets of protein kinase inhibitors. Journal of medicinal chemistry, 48(12), 4138-52. PMID: 15943486.

Thomas, A. S., Elcock, A. H. (2004). Molecular simulations suggest protein salt bridges are uniquely suited to life at high temperatures. Journal of the American Chemical Society, 126(7), 2208-14. PMID: 14971956.

Elcock, A. H. (2004). Molecular simulations of diffusion and association in multimacromolecular systems. Methods in enzymology, 383, 166-98. PMID: 15063651.

Yang, H., Elcock, A. H. (2003). Association lifetimes of hydrophobic amino acid pairs measured directly from molecular dynamics simulations. Journal of the American Chemical Society, 125(46), 13968-9. PMID: 14611227.

Morikis, D., Elcock, A. H., Jennings, P. A. & McCammon, J. A. (2003). The pH dependence of stability of the activation helix and the catalytic site of GART. Biophysical chemistry, 105(3-Feb), 279-91. PMID: 14499900.

Elcock, A. H. (2003). Atomic-level observation of macromolecular crowding effects: escape of a protein from the GroEL cage. Proceedings of the National Academy of Sciences of the United States of America, 100(5), 2340-4. PMID: 12601146.

Rockey, W. M., Elcock, A. H. (2002). Progress toward virtual screening for drug side effects. Proteins, 48(4), 664-71. PMID: 12211034.

Elcock, A. H. (2002). Atomistic simulations of competition between substrates binding to an enzyme. Biophysical journal, 82(5), 2326-32. PMID: 11964223.

Elcock, A. H. (2002). Modeling supramolecular assemblages. Current opinion in structural biology, 12(2), 154-60. PMID: 11959491.

Morikis, D., Elcock, A. H., Jennings, P. A. & McCammon, J. A. (2001). Native-state conformational dynamics of GART: a regulatory pH-dependent coil-helix transition examined by electrostatic calculations. Protein science : a publication of the Protein Society, 10(11), 2363-78. PMID: 11604542.

Morikis, D., Elcock, A. H., Jennings, P. A. & McCammon, J. A. (2001). Proton transfer dynamics of GART: the pH-dependent catalytic mechanism examined by electrostatic calculations. Protein science : a publication of the Protein Society, 10(11), 2379-92. PMID: 11604543.

Elcock, A. H. (2001). Prediction of functionally important residues based solely on the computed energetics of protein structure. Journal of molecular biology, 312(4), 885-96. PMID: 11575940.

Elcock, A. H., McCammon, J. A. (2001). Identification of protein oligomerization states by analysis of interface conservation. Proceedings of the National Academy of Sciences of the United States of America, 98(6), 2990-4. PMID: 11248019.

Elcock, A. H., McCammon, J. A. (2001). Calculation of weak protein-protein interactions: the pH dependence of the second virial coefficient. Biophysical journal, 80(2), 613-25. PMID: 11159430.

Elcock, A. H., Sept,, D. & McCammon, J. A. (2001). Computer simulation of protein-protein interactions.

Sept, D., Elcock, A. H. & McCammon, J. A. (1999). Computer simulations of actin polymerization can explain the barbed-pointed end asymmetry. Journal of molecular biology, 294(5), 1181-9. PMID: 10600376.

Elcock, A. H. (1999). Realistic modeling of the denatured states of proteins allows accurate calculations of the pH dependence of protein stability. Journal of molecular biology, 294(4), 1051-62. PMID: 10588906.

Elcock, A. H., Gabdoulline, R. R., Wade, R. C. & McCammon, J. A. (1999). Computer simulation of protein-protein association kinetics: acetylcholinesterase-fasciculin. Journal of molecular biology, 291(1), 149-62. PMID: 10438612.

Tara, S., Elcock, A. H., Kirchhoff, P. D., Briggs, J. M., Radic, Z., Taylor, P. & McCammon, J. A. (1998). Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorge. Biopolymers, 46(7), 465-74. PMID: 9838872.

Elcock, A. H. (1998). The stability of salt bridges at high temperatures: implications for hyperthermophilic proteins. Journal of molecular biology, 284(2), 489-502. PMID: 9813132.

Elcock, A. H., McCammon, J. A. (1998). Electrostatic contributions to the stability of halophilic proteins. Journal of molecular biology, 280(4), 731-48. PMID: 9677300.

Elcock, A. H., Huber, G. A. & McCammon, J. A. (1997). Electrostatic channeling of substrates between enzyme active sites: comparison of simulation and experiment. Biochemistry, 36(51), 16049-58. PMID: 9405038.

Fogolari, F., Elcock, A. H., Esposito, G., Viglino, P., Briggs, J. M. & McCammon, J. A. (1997). Electrostatic effects in homeodomain-DNA interactions. Journal of molecular biology, 267(2), 368-81. PMID: 9096232.

Elcock, A. H., McCammon, J. A. (1997). A continuum solvation model for studying protein hydration thermodynamics at high temperatures.

Elcock, A. H., Potter, M. J. & McCammon, J. A. (1997). Application of Poisson-Boltzmann solvation forces to macromolecular simulations in "Computer Simulation of Biomolecular Systems". Wilkinson, A.J., et al., Eds., ESCOM Science Publishers, B.V. Leiden, The Netherlands.

Elcock, A. H., McCammon, J. A. (1996). Evidence for electrostatic channeling in a fusion protein of malate dehydrogenase and citrate synthase. Biochemistry, 35(39), 12652-8. PMID: 8841108.

Elcock, A. H., Potter, M. J., Matthews, D. A., Knighton, D. R. & McCammon, J. A. (1996). Electrostatic channeling in the bifunctional enzyme dihydrofolate reductase-thymidylate synthase. Journal of molecular biology, 262(3), 370-4. PMID: 8845002.

Elcock, A. H., Rodger, A. & Richards, W. G. (1996). Theoretical studies of the intercalation of 9-hydroxyellipticine in DNA. Biopolymers, 39(3), 309-26. PMID: 8756512.

Antosiewicz,, J., Briggs,, J. M., Elcock, A. H., Gilson,, M. K. & McCammon, J. A. (1996). Computing ionization states of proteins with a detailed charge model.

Brooke-Taylor,, C. A., Grant,, G. H., Elcock, A. H. & Richards, W. G. (1996). Mechanism of action of antifreeze polypeptide HPLC6 in solution: Analysis of solvent behaviour by molecular dynamics.

Elcock, A. H., McCammon, J. A. (1996). The Low Dielectric Interior of Proteins is Sufficient to Cause Major Structural Changes in DNA on Association. Journal of the American Chemical Society, 118, 3787-3788.

Elcock, A. H., Lyne,, P. D., Mulholland,, A. J., Nandra,, A. & Richards, W. G. (1995). A Combined Quantum and Molecular Mechanical Study of DNA Cross-linking by Nitrous Acid. Journal of the American Chemical Society, 117, 4706-4707.

Elcock, A. H., McCammon, J. A. (1995). Sequence-dependent Hydration of DNA: Theoretical Results. Journal of the American Chemical Society, 117, 10161-10162.

Sanghani, S. R., Elcock, A. H. & Haworth, I. S. (1993). SUBCUR: visualization of structural differences between DNA duplexes. Journal of molecular graphics, 11(3), 211-3. PMID: 8110667.

Elcock, A. H., Richards,, W. G. (1993). Relative Hydration Free Energies of the Nucleic Acid Bases. Journal of the American Chemical Society, 115, 7930-7931.

Haworth, I. S., Elcock, A. H., Rodger, A. & Richards, W. G. (1991). A binding mode of lambda-[tris(1,10-phenanthroline)ruthenium(II)]2+ exhibiting preference for purine-3',5'-pyrimidine sites of DNA. Journal of biomolecular structure & dynamics, 9(3), 553-69. PMID: 1815643.

Haworth, I. S., Elcock, A. H., Freeman, J., Rodger, A. & Richards, W. G. (1991). Sequence selective binding to the DNA major groove: tris(1,10-phenanthroline) metal complexes binding to poly(dG-dC) and poly(dA-dT). Journal of biomolecular structure & dynamics, 9(1), 23-44. PMID: 1781946.