Analytical model for studying how environmental factors influence protein conformational stability in solution

Cheung, Jason K.; Raverkar, Prajakta S.; Truskett, Thomas M.
December 2006
Journal of Chemical Physics;12/14/2006, Vol. 125 Issue 22, p224903
Academic Journal
We introduce an analytical modeling strategy for probing the conformational stability of globular proteins in aqueous solution. In this approach, the intrinsic (i.e., infinite dilution) thermodynamic stability and coarse structural properties of the proteins, as well as the effective protein-protein interactions, derive from a heteropolymer collapse theory that incorporates predicted temperature- and pressure-dependent hydrophobic interactions. Protein concentration effects are estimated by integrating this information into a molecular thermodynamic model, which is an ad hoc generalization of the exact equilibrium theory of a one-dimensional binary mixture of square-well particles that interconvert through an isomerization (i.e., folding) reaction. The end result is an analytical multiscale modeling approach which, although still schematic, can predict that folded proteins exhibit a closed-loop region of stability in the pressure-temperature plane and that protein concentration has a nonmonotonic effect on protein stability, results consistent with qualitative trends observed in both experiments of protein solutions and simulations of coarse-grained protein models.


Related Articles

  • Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme. Jin Wang; Yong Wang; Xiakun Chu; Hagen, Stephen J.; Wei Han; Erkang Wang // PLoS Computational Biology;Apr2011, Vol. 7 Issue 4, p1 

    Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change - protein folding. In particular,...

  • Recent Progress and Future Directions in Protein-Protein Docking. Ritchie, David W. // Current Protein & Peptide Science;Feb2008, Vol. 9 Issue 1, p1 

    This article gives an overview of recent progress in protein-protein docking and it identifies several directions for future research. Recent results from the CAPRI blind docking experiments show that docking algorithms are steadily improving in both reliability and accuracy. Current docking...

  • Unravelling Hot Spots: a comprehensive computational mutagenesis study. Moreira, Irina; Fernandes, Pedro; Ramos, Maria // Theoretical Chemistry Accounts: Theory, Computation, & Modeling;Feb2007, Vol. 117 Issue 1, p99 

    As protein–protein interactions are critical for all biological functions, representing a large and important class of targets for human therapeutics, identification of protein–protein interaction sites and detection of specific amino acid residues that contribute to the...

  • Molecular Simulations of Rhodopsin Tetrameter. Witt, M.; Ciarkowski, J.; Czaplewski, C. // Protein & Peptide Letters;Apr2007, Vol. 14 Issue 4, p381 

    Di/oligomerization of G-protein coupled receptors (GPCRs) is well established, however very little is known regarding the interaction details. Current paper presents results of molecular dynamics simulations of theoretical model of rhodopsin tetramer with transducine (Gt) in lipid bilayer....

  • Molecular dynamics simulations of the Nip7 proteins from the marine deep- and shallow-water Pyrococcus species. Medvedev, Kirill; Alemasov, Nikolay; Vorobjev, Yuri; Boldyreva, Elena; Kolchanov, Nikolay; Afonnikov, Dmitry // BMC Structural Biology;2014, Vol. 14 Issue 1, p2 

    Background The identification of the mechanisms of adaptation of protein structures to extreme environmental conditions is a challenging task of structural biology. We performed molecular dynamics (MD) simulations of the Nip7 protein involved in RNA processing from the shallow-water (P....

  • NMRDyn: A Program for NMR Relaxation Studies of Protein Association. Wang, Conan K.; Schirra, Horst Joachim; Craik, David J. // PLoS ONE;2008, Vol. 3 Issue 11, p1 

    Self-association is an important biological phenomenon that is associated with many cellular processes. NMR relaxation measurements provide data about protein molecular dynamics at the atomic level and are sensitive to changes induced by self-association. Thus, measurements and analysis of NMR...

  • Modeling of Arylamide Helix Mimetics in the p53 Peptide Binding Site of hDM2 Suggests Parallel and Anti-Parallel Conformations Are Both Stable. Fuller, Jonathan C.; Jackson, Richard M.; Edwards, Thomas A.; Wilson, Andrew J.; Shirts, Michael R.; Verma, Chandra // PLoS ONE;Aug2012, Vol. 7 Issue 8, Special section p1 

    The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement...

  • Gap discrete breathers in a two-component two-dimensional crystal in thermal equilibrium. Dmitriev, S.; Khadeeva, L. // Physics of the Solid State;Jul2011, Vol. 53 Issue 7, p1425 

    Crystals having a gap in the phonon spectrum can maintain gap discrete breathers (DBs), i.e., nonlinear localized oscillatory modes existing in the absence of defects and having a frequency lying in the gap. The lifetime of gap DBs in a two-dimensional perfect crystal of the composition A B in...

  • ATOMISTIC SIMULATIONS OF SHOCK-INDUCED PHASE TRANSFORMATIONS IN POLYCRYSTALLINE IRON. Kadau, Kai; Germann, Timothy C.; Lomdahl, Peter S.; Albers, Robert C.; Wark, Justin S.; Higginbotham, Andrew; Holian, Brad Lee // AIP Conference Proceedings;12/12/2007, Vol. 955 Issue 1, p313 

    We report on large-scale non-equilibrium atomistic simulations of shock-induced transformations in polycrystalline iron samples. These simulations show that, depending on the crystallographic orientation of the body-centered-cubic (bcc) parent phase grains with respect to the shock direction, a...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics