Michael J. Schnieders, DSc

Portrait
Associate Professor of Biochemistry
Associate Professor of Biomedical Engineering (BME)

Contact Information

Fax
319-335-5631

Office
5013 Seamans Center for the Engineering Arts and Sciences
Iowa City, IA 52242
650-995-3526

Primary Office
4-516 Bowen Science Building
Iowa City, IA 52242
650-995-3526

Lab
4-514 Bowen Science Building
Iowa City, IA 52242
650-995-3526

Education

DSc, Biomedical Engineering, Washington University in St. Louis
Postdoctoral Fellow, Chemistry, Stanford University
Postdoctoral Fellow, Biomedical Engineering, The University of Texas

Education/Training Program Affiliations

Department of Biochemistry PhD, Department of Pharmacology Graduate Program, Interdisciplinary Graduate Program in Informatics, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center for Biocatalysis and Bioprocessing, Center for Bioinformatics and Computational Biology, Holden Comprehensive Cancer Center, Institute for Vision Research, Iowa Institute of Human Genetics.

Research Summary

Our lab is focused on molecular biophysics theory and high performance computational algorithms that are needed to reduce the time and cost of engineering drugs and organic biomaterials. A complementary goal is to help open the door to personalized medicine by developing tools to map genetic information onto molecular phenotypes.

1. Next Generation Macromolecular X-ray Crystallography X-ray crystallography is a critical experimental method used by biochemists to determine the structure and function of the biomolecular foundations of medicine. We have recently demonstrated that the chemical information contained in a polarizable force field called AMOBEA significantly improves DNA and protein structures compared to X-ray refinements done with previous generation theory. We are now working to model experimental X-ray diffraction data as an ensemble using Bayesian inference.

2. Prediction of the Structure, Thermodynamics and Solubility of Drug Tablets Important unsolved problems for the engineering of organic biomaterials include prediction of their structure, thermodynamic stability and solubility from first principles. Solubility is the saturating concentration of a molecule within a liquid solvent, where the physical process consists of solvated molecules in equilibrium with their solid phase. We have developed the first consistent procedure for the prediction of the structure, thermodynamic stability, and solubility of organic crystals using molecular dynamics simulations. Currently the methodology is being extended to predict the properties for a range of organic crystals, including both pharmaceuticals and peptide models of neurological aggregation diseases.

3. Personalized Medicine: From Genome Sequencing to Molecular Phenotypes Since 2001, the cost to sequence a patient’s genome has fallen from $100 million to approximately $1,000. The rapid achievement of affordable genetic information is outpacing our ability to fully capitalize on opportunities to provide personalized healthcare. To help address this challenge, we are collaborating with The University of Iowa Center for Bioinformatics and Computational Biology to develop tools that tightly couple bioinformatics to the computational prediction of biomolecular structure, thermodynamics and kinetics.

4. Biomolecular Electrostatics and High-Performance Computing Application such as X-ray crystallography refinement, biomaterials thermodynamics and personalized medicine depend on an accurate, efficient description of molecular energetics. Our lab contributes a parallelized molecular biophysics computer code called Force Field X that includes novel biomolecular electrostatics algorithms such as particle-mesh Ewald with support for space group symmetry and the generalized Kirkwood implicit solvent model.

Publications

Rackers, J. A., Wang, Z., Lu, C., Laury, M. L., Lagardère, L., Schnieders, M. J., Piquemal, J. P., Ren, P. & Ponder, J. W. (2018). Tinker 8: Software Tools for Molecular Design. Journal of Chemical Theory and Computation, 14(10), 5273-5289. PMID: 30176213.

Azaiez, H., Booth, K. T., Ephraim, S. S., Crone, B., Black-Ziegelbein, E. A., Marini, R. J., Shearer, A. E., Sloan-Heggen, C. M., Kolbe, D., Casavant, T., Schnieders, M. J., Nishimura, C., Braun, T. & Smith, R. J. (2018). Genomic Landscape and Mutational Signatures of Deafness-Associated Genes. American Journal of Human Genetics, 103(4), 484-497. PMID: 30245029.

Schnieders, M. J., Goar, W., Griess, M., Roos, B. R., Scheetz, T. E., Stone, E. M. & Fingert, J. H. (2018). A novel mutation (LEU396ARG) in OPA1 is associated with a severe phenotype in a large dominant optic atrophy pedigree. Eye, 32(4), 843-845. PMID: 29350691.

Lagardère, L., Jolly, L. H., Lipparini, F., Aviat, F., Stamm, B., Jing, Z. F., Harger, M., Torabifard, H., Cisneros, G. A., Schnieders, M. J., Gresh, N., Maday, Y., Ren, P. Y., Ponder, J. W. & Piquemal, J. P. (2018). Tinker-HP: A massively parallel molecular dynamics package for multiscale simulations of large complex systems with advanced point dipole polarizable force fields. Chemical Science, 9(4), 956-972. DOI: 10.1039/c7sc04531j.

Lansdon, L. A., Bernabe, H. V., Nidey, N., Standley, J., Schnieders, M. J. & Murray, J. C. (2017). The Use of Variant Maps to Explore Domain-Specific Mutations of FGFR1. Journal of Dental Research, 96(11), 1339-1345. DOI: 10.1177/0022034517726496.

Simpson, A., Avdic, A., Roos, B. R., DeLuca, A., Miller, K., Schnieders, M. J., Scheetz, T. E., Alward, W. L. & Fingert, J. H. (2017). LADD syndrome with glaucoma is caused by a novel gene. Molecular Vision, 23, 179-184.

Bell, D. R., Qi, R., Jing, Z., Xiang, J. Y., Mejias, C., Schnieders, M. J., Ponder, J. W. & Ren, P. (2016). Calculating binding free energies of host-guest systems using the AMOEBA polarizable force field. Physical Chemistry Chemical Physics, 18(44), 30261-30269. DOI: 10.1039/C6CP02509A.

Bu, F., Borsa, N. G., Jones, M. B., Takanami, E., Nishimura, C., Hauer, J. J., Azaiez, H., Black-Ziegelbein, E. A., Meyer, N. C., Kolbe, D. L., Li, Y., Frees, K., Schnieders, M. J., Thomas, C., Nester, C. & Smith, R. J. (2016). High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 Glomerulopathies. Journal of the American Society of Nephrology, 27(4), 1245-1253. DOI: 10.1681/asn.2015040385.

DeLuca, A. P., Whitmore, S. S., Barnes, J., Sharma, T. P., Westfall, T. A., Scott, C. A., Weed, M. C., Wiley, J. S., Wiley, L. A., Johnston, R. M., Schnieders, M. J., Lentz, S. R., Tucker, B. A., Mullins, R. F., Scheetz, T. E., Stone, E. M. & Slusarski, D. C. (2016). Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis. Human Molecular Genetics, 25(1), 44-56. DOI: 10.1093/hmg/ddv446.

Nessler, I. J., Litman, J. M. & Schnieders, M. J. (2016). Toward polarizable AMOEBA thermodynamics at fixed charge efficiency using a dual force field approach: application to organic crystals. Physical Chemistry Chemical Physics, 18(44), 30313-30322. DOI: 10.1039/C6CP02595A.

Booth, K. T., Azaiez, H., Kahrizi, K., Simpson, A. C., Tollefson, W. T., Sloan, C. M., Meyer, N. C., Babanejad, M., Ardalani, F., Arzhangi, S., Schnieders, M. J., Najmabadi, H. & Smith, R. J. (2015). PDZD7 and hearing loss: More than just a modifier. American Journal of Medical Genetics Part A. DOI: 10.1002/ajmg.a.37274.

LuCore, S. D., Litman, J. M., Powers, K. T., Gao, S., Lynn, A. M., Tollefson, W. T., Fenn, T. D., Washington, M. T. & Schnieders, M. J. (2015). Dead-end elimination with a polarizable force field repacks PCNA structures. Biophysical Journal, 109(4), 816-826. DOI: 10.1016/j.bpj.2015.06.062.

Ren, P., Chun, J., Thomas, D. G., Schnieders, M. J., Marucho, M., Zhang, J. & Baker, N. A. (2012). Biomolecular electrostatics and solvation: a computational perspective. Quarterly Reviews of Biophysics, 45(4), 427-491. PMID: 23217364.

Schnieders, M. J., Kaoud, T. S., Yan, C., Dalby, K. N. & Ren, P. (2012). Computational insights for the discovery of non-ATP competitive inhibitors of MAP kinases. Current Pharmaceutical Design, 18(9), 1173-1185. PMID: 22316156.

Fenn, T. D., Schnieders, M. J. (2011). Polarizable atomic multipole X-ray refinement: weighting schemes for macromolecular diffraction. Acta Crystallographica Section D, 67(11), 957-965. PMID: 22101822.

MacCallum, J. L., Pérez, A., Schnieders, M. J., Hua, L., Jacobson, M. P. & Dill, K. A. (2011). Assessment of protein structure refinement in CASP9. Proteins: Structure, Function, and Bioinformatics, 79(S10), 74-90. PMID: 22069034.

Fenn, T. D., Schnieders, M. J., Mustyakimov, M., Wu, C., Langan, P., Pande, V. S. & Brunger, A. T. (2011). Reintroducing electrostatics into macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration. Structure, 19(4), 523-533. PMID: 21481775.

Schnieders, M. J., Fenn, T. D. & Pande, V. S. (2011). Polarizable atomic multipole X-ray refinement: Particle mesh Ewald electrostatics for macromolecular crystals. Journal of Chemical Theory and Computation, 7(4), 1141-1156. DOI: 10.1021/ct100506d.

Fenn, T. D., Schnieders, M. J., Brunger, A. T. & Pande, V. S. (2010). Polarizable atomic multipole x-ray refinement: hydration geometry and application to macromolecules. Biophysical Journal, 98(12), 2984-2992. PMID: 20550911.

Mathew-Fenn, R. S., Das, R., Fenn, T. D., Schnieders, M. J. & Harbury, P. (2009). Response to comment on "Remeasuring the double helix". Science, 325(5940), 538. DOI: 10.1126/science.1168876.

MacCallum, J. L., Hua, L., Schnieders, M. J., Pande, V. S., Jacobson, M. P. & Dill, K. A. (2009). Assessment of the protein-structure refinement category in CASP8. Proteins: Structure, Function, and Bioinformatics, 77(S9), 66-80. PMID: 19714776.

Shi, Y., Jiao, D., Schnieders, M. J. & Ren, P. (2009). Trypsin-ligand binding free energy calculation with AMOEBA. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, 2009, 2328-31. PMID: 19965178.

Schnieders, M. J., Fenn, T. D., Pande, V. S. & Brunger, A. T. (2009). Polarizable atomic multipole X-ray refinement: Application to peptide crystals. Acta Crystallographica Section D, 65(9), 952-965. DOI: 10.1107/S0907444909022707.

Jiao, D., Zhang, J. J., Duke, R. E., Li, G. H., Schnieders, M. J. & Ren, P. (2009). Trypsin-ligand binding free energies from explicit and implicit solvent simulations with polarizable potential. Journal of Computational Chemistry, 30(11), 1701-1711. DOI: 10.1002/jcc.21268.

Schnieders, M. J., Ponder, J. W. (2007). Polarizable atomic multipole solutes in a generalized Kirkwood continuum. Journal of Chemical Theory and Computation, 3(6), 2083-2097. DOI: 10.1021/ct7001336.

Schnieders, M. J., Baker, N. A., Ren, P. & Ponder, J. W. (2007). Polarizable atomic multipole solutes in a Poisson-Boltzmann continuum. Journal of Chemical Physics, 126(12), 124114. DOI: 10.1063/1.2714528.

Anderson, D. A., Schnieders, M. J., Heiner, A. D., Pederson, D. R., Brown, T. D. & Brand, R. A. (1999). A surgical guide to accurately place pins or nails within the femoral head. Journal of Musculoskeletal Research, 3, 233-237. DOI: 10.1142/S0218957799000245.

Schnieders, M. J., Dave, S. B., Morrow, D. E., Heiner, A. D., Pedersen, D. R. & Brown, T. D. (1997). Assessing the accuracy of a prototype drill guide for fibular graft placement in femoral head necrosis. Iowa Orthopaedic Journal, 17, 58-63.