ArticleProteins2011
Predicting extreme pKa shifts in staphylococcal nuclease mutants with constant pH molecular dynamics.
Article in Proteins, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Benchmark Study for Calculations of pKa Values of Metal Ligands in Proteins.Journal of chemical theory and computation · 2026Article
- PKAD-R: curated, redesigned and expanded database of experimental pKa values in proteins.Journal of computational biophysics and chemistry · 2025Article
- Simultaneous Construction of Free Energy Surfaces via Multisite λ Dynamics and Umbrella Sampling.Journal of chemical theory and computation · 2025Article
- Adding the AMBER 14SB Force Field to the Stochastic Titration CpHMD Method.Journal of chemical theory and computation · 2025Article
- Constant pH Simulation with FMM Electrostatics in GROMACS. (A) Design and Applications.Journal of chemical theory and computation · 2025Article
- AMOEBA Force Field Predicts Accurate Hydrogen Bond Counts of Nitriles in SNase by Revealing Water-Protein Interaction in Vibrational Absorption Frequencies.The journal of physical chemistry. B · 2023Article
- Protein pJournal of chemical theory and computation · 2022Article
- Prediction of protein pChemical science · 2022Article
- Quantitative Analysis of Protein Unfolded State Energetics: Experimental and Computational Studies Demonstrate That Non-Native Side-Chain Interactions Stabilize Local Native Backbone Structure.The journal of physical chemistry. B · 2021Article
- 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
- Reservoir pH replica exchange.The Journal of chemical physics · 2018Article
- Origin of pKThe journal of physical chemistry. B · 2017Article
- Efficient implementation of constant pH molecular dynamics on modern graphics processors.Journal of computational chemistry · 2016Article
- The Role of Electrostatic Interactions in Folding of β-Proteins.Journal of the American Chemical Society · 2016Article
- Constant-pH Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulation Method.Journal of chemical theory and computation · 2015Article
- Membrane environment modulates the pKa values of transmembrane helices.The journal of physical chemistry. B · 2015Article
- Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Effects of system net charge and electrostatic truncation on all-atom constant pH molecular dynamics.Journal of computational chemistry · 2014Article
- Constant pH molecular dynamics of proteins in explicit solvent with proton tautomerism.Proteins · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Accurate computational methods of determining protein and nucleic acid pK(a) values are vital to understanding pH-dependent processes in biological systems. In this article, we use the recently developed method constant pH molecular dynamics (CPHMD) to explore the calculation of highly perturbed pK(a) values in variants of staphylococcal nuclease (SNase). Simulations were performed using the replica exchange (REX) protocol for improved conformational sampling with eight temperature windows, and yielded converged proton populations in a total sampling time of 4 ns. Our REX-CPHMD simulations resulted in calculated pK(a) values with an average unsigned error (AUE) of 0.75 pK units for the acidic residues in Δ + PHS, a hyperstable variant of SNase. For highly pK(a)-perturbed SNase mutants with known crystal structures, our calculations yielded an AUE of 1.5 pK units and for those mutants based on modeled structures an AUE of 1.4 pK units was found. Although a systematic underestimate of pK shifts was observed in most of the cases for the highly perturbed pK mutants, correlations between conformational rearrangement and plasticity associated with the mutation and error in pK(a) prediction was not evident in the data. This study further extends the scope of electrostatic environments explored using the REX-CPHMD methodology and suggests that it is a reliable tool for rapidly characterizing ionizable amino acids within proteins even when modeled structures are employed.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.