ArticleBiophysical journal2010
Uncovering specific electrostatic interactions in the denatured states of proteins.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Force Field Limitations of All-Atom Continuous Constant pH Molecular Dynamics.The journal of physical chemistry. B · 2024Article
- Exploring pH Dependent Host/Guest Binding Affinities.The journal of physical chemistry. B · 2020Article
- M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Generalized Born Based Continuous Constant pH Molecular Dynamics in Amber: Implementation, Benchmarking and Analysis.Journal of chemical information and modeling · 2018Article
- Electrostatic Interactions in Protein Structure, Folding, Binding, and Condensation.Chemical reviews · 2018Review
- pH-Dependent cooperativity and existence of a dry molten globule in the folding of a miniprotein BBL.Physical chemistry chemical physics : PCCP · 2018Article
- Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models.Biophysical journal · 2018Article
- Proton-Coupled Conformational Allostery Modulates the Inhibitor Selectivity for β-Secretase.The journal of physical chemistry letters · 2017Article
- The N-Terminal Domain of Ribosomal Protein L9 Folds via a Diffuse and Delocalized Transition State.Biophysical journal · 2017Article
- The effect of chirality and steric hindrance on intrinsic backbone conformational propensities: tools for protein design.Protein engineering, design & selection : PEDS · 2016Article
- Nascent β-Hairpin Formation of a Natively Unfolded Peptide Reveals the Role of Hydrophobic Contacts.Biophysical journal · 2015Article
- Conformational Dynamics of Two Natively Unfolded Fragment Peptides: Comparison of the AMBER and CHARMM Force Fields.The journal of physical chemistry. B · 2015Article
- Membrane environment modulates the pKa values of transmembrane helices.The journal of physical chemistry. B · 2015Article
- Constant pH molecular dynamics of proteins in explicit solvent with proton tautomerism.Proteins · 2014Article
- pH-sensitive residues in the p19 RNA silencing suppressor protein from carnation Italian ringspot virus affect siRNA binding stability.Protein science : a publication of the Protein Society · 2013Article
- pH-dependent dynamics of complex RNA macromolecules.Journal of chemical theory and computation · 2013Article
- Unraveling A Trap-and-Trigger Mechanism in the pH-Sensitive Self-Assembly of Spider Silk Proteins.The journal of physical chemistry letters · 2012Article
- Constant pH Molecular Dynamics Simulations of Nucleic Acids in Explicit Solvent.Journal of chemical theory and computation · 2012Article
- Differential ordering of the protein backbone and side chains during protein folding revealed by site-specific recombinant infrared probes.Journal of the American Chemical Society · 2011Article
- Insights into the structural stability of Bax from molecular dynamics simulations at high temperatures.Protein science : a publication of the Protein Society · 2011Article
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1 author.
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Abstract
The stability and folding of proteins are modulated by energetically significant interactions in the denatured state that is in equilibrium with the native state. These interactions remain largely invisible to current experimental techniques, however, due to the sparse population and conformational heterogeneity of the denatured-state ensemble under folding conditions. Molecular dynamics simulations using physics-based force fields can in principle offer atomistic details of the denatured state. However, practical applications are plagued with the lack of rigorous means to validate microscopic information and deficiencies in force fields and solvent models. This study presents a method based on coupled titration and molecular dynamics sampling of the denatured state starting from the extended sequence under native conditions. The resulting denatured-state pK(a)s allow for the prediction of experimental observables such as pH- and mutation-induced stability changes. I show the capability and use of the method by investigating the electrostatic interactions in the denatured states of wild-type and K12M mutant of NTL9 protein. This study shows that the major errors in electrostatics can be identified by validating the titration properties of the fragment peptides derived from the sequence of the intact protein. Consistent with experimental evidence, our simulations show a significantly depressed pK(a) for Asp(8) in the denatured state of wild-type, which is due to a nonnative interaction between Asp(8) and Lys(12). Interestingly, the simulation also shows a nonnative interaction between Asp(8) and Glu(48) in the denatured state of the mutant. I believe the presented method is general and can be applied to extract and validate microscopic electrostatics of the entire folding energy landscape.
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