The primary goal of this proposal is to provide a molecular picture of the basis for the profound effects of cellular crowding and nonideal solution effects in general on biology via the development of new theoretical techniques in conjunction with simulation to provide a molecular picture (theory) of the aspects of the free energy surface that govern protein interfaces and associations in solution. In this project we will produce a molecular picture (theory) of protein interfaces and properties in nonideal solution which are consistent with known and coming thermodynamic and structural data. Test cases including Sm endonuclease and insulin and applications have been chosen to maximize overlap with existing data or collaborations that will yield data of specific relevance to our goal. We will make extensive use of concentration variables in our theoretical and computational studies. Biology rarely uses temperature differences as a mechanism to drive processes; nature more often uses solution composition (concentration of salt, osmolytes, other biomolecules, etc) to affect changes in biological conformation and state of aggregation. We seek to provide a better understanding of these effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037657-17
Application #
7337155
Study Section
Macromolecular Structure and Function B Study Section (MSFB)
Program Officer
Wehrle, Janna P
Project Start
1988-08-01
Project End
2010-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
17
Fiscal Year
2008
Total Cost
$223,500
Indirect Cost
Name
University of Houston
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
036837920
City
Houston
State
TX
Country
United States
Zip Code
77204
Seckfort, Danielle; Montgomery Pettitt, B (2018) Price of disorder in the lac repressor hinge helix. Biopolymers :e23239
Dai, Wei; Chen, Muyuan; Myers, Christopher et al. (2018) Visualizing Individual RuBisCO and Its Assembly into Carboxysomes in Marine Cyanobacteria by Cryo-Electron Tomography. J Mol Biol 430:4156-4167
Drake, Justin A; Pettitt, B Montgomery (2018) Thermodynamics of Conformational Transitions in a Disordered Protein Backbone Model. Biophys J 114:2799-2810
Sarma, Rahul; Wong, Ka-Yiu; Lynch, Gillian C et al. (2018) Peptide Solubility Limits: Backbone and Side-Chain Interactions. J Phys Chem B 122:3528-3539
Kolawole, Abimbola O; Smith, Hong Q; Svoboda, Sophia A et al. (2017) Norovirus Escape from Broadly Neutralizing Antibodies Is Limited to Allostery-Like Mechanisms. mSphere 2:
Zhang, Cheng; Drake, Justin A; Ma, Jianpeng et al. (2017) Optimal updating magnitude in adaptive flat-distribution sampling. J Chem Phys 147:174105
Asthagiri, D; Karandur, Deepti; Tomar, Dheeraj S et al. (2017) Intramolecular Interactions Overcome Hydration to Drive the Collapse Transition of Gly15. J Phys Chem B 121:8078-8084
Ou, Shu-Ching; Drake, Justin A; Pettitt, B Montgomery (2017) Nonpolar Solvation Free Energy from Proximal Distribution Functions. J Phys Chem B 121:3555-3564
Tomar, Dheeraj S; Weber, Valéry; Pettitt, B Montgomery et al. (2016) Importance of Hydrophilic Hydration and Intramolecular Interactions in the Thermodynamics of Helix-Coil Transition and Helix-Helix Assembly in a Deca-Alanine Peptide. J Phys Chem B 120:69-76
Karandur, D; Pettitt, B M (2016) The contribution of electrostatic interactions to the collapse of oligoglycine in water. Condens Matter Phys 19:

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