ArticlePLoS computational biology2012
pH-Dependent conformational changes in proteins and their effect on experimental pK(a)s: the case of Nitrophorin 4.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Constrained diffusion-enabled construction of a highly expressed and robust peptide asparaginyl ligase.Chemical science · 2026Article
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- Decoding pH-dependent structural dynamics of CHIKV nsP2 protease: insights from computational antiviral targeting.Molecular diversity · 2026Article
- Ecotoxicity assessment of dairy wastewater: environmental risks and regulatory needs.Ecotoxicology (London, England) · 2026Article
- Exploration of Natural Protein-Polysaccharide-Polyphenol Ternary Complexes from Grape Pomace for Clean-Label Pickering Emulsions Through pH Adjustment.Foods (Basel, Switzerland) · 2026Article
- TrIPP: a trajectory iterative pKa predictor.Bioinformatics (Oxford, England) · 2026Article
- Deep Learning-Based Prediction of Enzyme Optimal pH and Design of Point Mutations to Improve Acid Resistance.ACS synthetic biology · 2025Article
- Intracellular pH regulates ubiquitin-mediated degradation of the MAP kinase ERK3.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Revealing pH-dependent antimicrobial peptide, GL13K, characteristics: A constant pH molecular dynamics study.bioRxiv : the preprint server for biology · 2025Article
- Silk protein discoidal microparticles for site-specific delivery of docetaxel in metastatic lung cancer.Materials today. Bio · 2025Article
- Molecular Cloning, Optimization of Expression and Functional Characterization of the Global Transcriptional Regulator MosR (Rv0348) of Mycobacterium tuberculosis.Applied biochemistry and biotechnology · 2025Article
- Beyond static structures: protein dynamic conformations modeling in the post-AlphaFold era.Briefings in bioinformatics · 2025Review
- A Universal Approach to Anchoring Chromophores onto Magnetic Scaffold for Achieving Easily Recyclable Heterogeneous Photocatalytic Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Protonation Effects in Protein-Ligand Complexes - A Case Study of Endothiapepsin and Pepstatin A with Computational and Experimental Methods.ChemMedChem · 2025Article
- Constant pH Simulation with FMM Electrostatics in GROMACS. (A) Design and Applications.Journal of chemical theory and computation · 2025Article
- Improved Structure-Based Histidine pJournal of chemical information and modeling · 2025Article
- The role of ribosomal protein networks in ribosome dynamics.Nucleic acids research · 2025Article
- Discovery of alkaline laccases from basidiomycete fungi through machine learning-based approach.Biotechnology for biofuels and bioproducts · 2024Article
- Assessing pH-Dependent Conformational Changes in the Fusion Peptide Proximal Region of the SARS-CoV-2 Spike Glycoprotein.Viruses · 2024Article
- Cellular and epigenetic perspective of protein stability and its implications in the biological system.Epigenomics · 2024Review
1 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
The acid-base behavior of amino acids is an important subject of study due to their prominent role in enzyme catalysis, substrate binding and protein structure. Due to interactions with the protein environment, their pK(a)s can be shifted from their solution values and, if a protein has two stable conformations, it is possible for a residue to have different "microscopic", conformation-dependent pK(a) values. In those cases, interpretation of experimental measurements of the pK(a) is complicated by the coupling between pH, protonation state and protein conformation. We explored these issues using Nitrophorin 4 (NP4), a protein that releases NO in a pH sensitive manner. At pH 5.5 NP4 is in a closed conformation where NO is tightly bound, while at pH 7.5 Asp30 becomes deprotonated, causing the conformation to change to an open state from which NO can easily escape. Using constant pH molecular dynamics we found two distinct microscopic Asp30 pK(a)s: 8.5 in the closed structure and 4.3 in the open structure. Using a four-state model, we then related the obtained microscopic values to the experimentally observed "apparent" pK(a), obtaining a value of 6.5, in excellent agreement with experimental data. This value must be interpreted as the pH at which the closed to open population transition takes place. More generally, our results show that it is possible to relate microscopic structure dependent pKa values to experimentally observed ensemble dependent apparent pK(a)s and that the insight gained in the relatively simple case of NP4 can be useful in several more complex cases involving a pH dependent transition, of great biochemical interest.
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