Interfacial Properties of Biomolecular Systems:Mechanism and Kinetics of Association and Melting
EMSL Project ID
34896
Abstract
The details of biomolecular recognition and interfacial interactions are integral components in association and dissociation and are fundamental to many aspects of biology and biotechnology. Missing are the molecular descriptions. For example, in the past, this laboratory has modeled DNA melting thermally, heating the systems to temperatures that would ensure duplex separation. But, in nature, the melting of DNA is not driven by heat; rather, enzymes and other proteins drive this process by shielding the molecule from the solvent and ions. In the case of the enzyme topoisomerase, the fundamental topological of the DNA is altered, the linking number Lk, i.e., the underwinding or overwinding of the DNA. The molecules find each other and function in complex and highly crowded environments. Recognition between the species occurs followed by binding, both specific and non-specific. In this project the focus will be on the kinetics and mechanism of the interfacial interactions of: i) the melting/dissociation of oligonucleotide systems, stress versus heat, ii) biomolecular association, the recognition and association of a protein/DNA system, and iii) atomic level description of RNA hairpin folding. All-atom molecular dynamics simulations will be used to study the melting of DNA. For the stress studies the calculations will be composed of a DNA duplex with at least three complete turns, in solution. Periodic boundary conditions will be used to connect the ends of the duplex at the edge of the simulation box and the linking number is altered by either adding base pairs to underwind the DNA or removing base pairs to overwind relative to the relaxed structure. The now familiar multiscale approach which uses data from calculations on a shorter length and time scale as input parameter for simulations at a longer time scale will be used to study the protein-DNA association. Brownian dynamics simulations coupled with all-atom molecular dynamics simulations will be used to understand the protein recognition and binding with DNA. Finally, the RNA hairpin folding studies will be performed with temperature-dependent replica exchange molecular dynamics simulations.
Project Details
Project type
Capability Research
Start Date
2009-10-01
End Date
2012-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Ambia Garrido J, A Vainrub, and BM Pettitt. 2010. "A Model for Structure and Thermodynamics of ssDNA and dsDNA Near a Surface: A Coarse Grained Approach." Computer Physics Communications 181:2001-2007. doi:10.1016/j.cpc.2010.08.029
Ambia Garrido J, A Vainrub, and BM Pettitt. 2011. "Free Energy Considerations for Nucleic Acids with Dangling Ends Near a Surface: a Coarse Grained Approach." Journal of Physics. Condensed Matter 23(32):325101. doi:10.1088/0953-8984/23/32/325101
Chen C, and BM Pettitt. 2011. "The Binding Process of a Nonspecific Enzyme with DNA." Biophysical Journal 101(5):1139–1147. doi:10.1016/j.bpj.2011.07.016
Chen C ,Pettitt B M 2016. "DNA Shape versus Sequence Variations in the Protein Binding Process" Biophysical Journal 110(3):534–544. 10.1016/j.bpj.2015.11.3527
Dyer K M,Pettitt B M 2013. "Proximal Distributions from Angular Correlations: A Measure of the Onset of Coarse-graining" Journal of Chemical Physics 139():214111. 10.1063/1.4832895
Hu CY, GC Lynch, H Kokubo, and BM Pettitt. 2010. "Trimethylamine ?-oxide Influence on the Backbone of Proteins: An Oligoglycine Model." Proteins. Structure, Function, and Bioinformatics 78(3):695-704. doi:10.1002/prot.22598
Hu CY, H Kokubo, GC Lynch, DW Bolen, and BM Pettitt. 2010. "Backbone Additivity in the Transfer Model of Protein Salvation." Protein Science 19(5):1011-1022. doi:10.1002/pro.378
Kokubo H, CY Hu, and BM Pettitt. 2011. "Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine." Journal of the American Chemical Society 133(6):1849 - 1858. doi:10.1021/ja1078128
Lin B, and BM Pettitt. 2011. "Electrostatic Solvation Free Energy of Amino Acid Side Chain Analogs: Implications for the Validity of Electrostatic Linear Response in Water." Journal of Computational Chemistry 32(5):878-885. doi:10.1002/jcc.21668
Lin B, and BM Pettitt. 2011. "Note: On the Universality of Proximal Radial Distribution Functions of Proteins." Journal of Chemical Physics 134(10):106101 - 106102. doi:10.1063/1.3565035
Lin B, KY Wong, CY Hu, H Kokubo, and BM Pettitt. 2011. "Fast Calculations of Electrostatic Solvation Free Energy from Reconstructed Solvent Density Using Proximal Radial Distribution Functions." The Journal of Physical Chemistry Letters 2(13):1626-1632. doi:10.1021/jz200609v
Perkyns JS, GC Lynch, JJ Howard, and BM Pettitt. 2010. "Protein Solvation from Theory and Simulation: Exact Treatment of Coulomb Interactions in Three-Dimensional Theories." Journal of Chemical Physics 132(6):064106. doi:10.1063/1.3299277
Perkyns JS, GC Lynch, JJ Howard, and BM Pettitt. 2010. "Protein Solvation from Theory and Simulation: Exact Treatment of Coulomb Interactions in Three-Dimensional Theories." Journal of Chemical Physics 132(6):064106. doi:10.1063/1.3299277
Wong KY, and BM Pettitt. 2008. "The Pathway of Oligomeric DNA Melting Investigated by Molecular Dynamics Simulations." Biophysical Journal 95:5618–5626. doi:10.1529/biophysj.108.141010