ArticleProteins2013
Capturing the energetics of water insertion in biological systems: the water flooding approach.
Article in Proteins, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
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- Novel Insights into the Catalytic Mechanism of Collagenolysis by Zn(II)-Dependent Matrix Metalloproteinase-1.Biochemistry · 2024Article
- Efficient Sampling of Cavity Hydration in Proteins with Nonequilibrium Grand Canonical Monte Carlo and Polarizable Force Fields.Journal of chemical theory and computation · 2024Article
- Water Networks in Complexes between Proteins and FDA-Approved Drugs.Journal of chemical information and modeling · 2023Article
- The catalytic mechanism of the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2).PLoS computational biology · 2022Article
- Electronic Polarization Is Essential for the Stabilization and Dynamics of Buried Ion Pairs in Staphylococcal Nuclease Mutants.Journal of the American Chemical Society · 2022Article
- Biomolecular QM/MM Simulations: What Are Some of the "Burning Issues"?The journal of physical chemistry. B · 2021Article
- Artificial Photosynthesis: Is Computation Ready for the Challenge Ahead?Nanomaterials (Basel, Switzerland) · 2021Review
- Revisiting the protomotive vectorial motion of FProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Validating the Water Flooding Approach by Comparing It to Grand Canonical Monte Carlo Simulations.The journal of physical chemistry. B · 2017Article
- Exploring the Drug Resistance of HCV Protease.The journal of physical chemistry. B · 2017Article
- Article
- Simulating the Function of the MjNhaP1 Transporter.The journal of physical chemistry. B · 2016Article
- Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer.Scientific reports · 2016Article
- Stay Wet, Stay Stable? How Internal Water Helps the Stability of Thermophilic Proteins.The journal of physical chemistry. B · 2015Article
- Photosynthetic diode: electron transport rectification by wetting the quinone cofactor.Physical chemistry chemical physics : PCCP · 2015Article
- Role of Internal Water on Protein Thermal Stability: The Case of Homologous G Domains.The journal of physical chemistry. B · 2015Article
- Hydrated Excess Protons Can Create Their Own Water Wires.The journal of physical chemistry. B · 2015Article
- Microscopic basis for kinetic gating in Cytochrome c oxidase: insights from QM/MM analysis.Chemical science · 2015Article
- Molecular simulation of water and hydration effects in different environments: challenges and developments for DFTB based models.The journal of physical chemistry. B · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Consistent description of the effect of internal water in proteins has been a major challenge for both simulation and experimental studies. Describing this effect has been particularly important and elusive in cases of charges in protein interiors. Here, we present a new microscopic method that provides an efficient way for simulating the energetics of water insertion. Instead of performing explicit Monte Carlo (MC) moves on the insertion process, which generally involves an enormous number of rejected attempts, our method is based on generating trial configurations with excess amount of internal water, estimating the relevant free energy by the linear response approximation, and then using a postprocessing MC treatment to filter out a limited number of configurations from a large possible set. Our approach is validated on particularly challenging test cases including the pK(a) of the V66D mutation in Staphylococcal nuclease, Glu286 in cytochrome c oxidase (CcO) and the energetics of a protonated water molecule in the D channel of CcO. The new postprocessing method allows us to reproduce the relevant energetics of highly unstable charges in protein interiors using fully microscopic calculations and provides a substantial improvement over regular microscopic free energy estimates. This advance established the effectiveness of our water insertion strategy in challenging cases that have not been addressed successfully by other microscopic methods. Furthermore, our study provides a new exciting view on the crucial effect of water penetration in key biological systems as well as a new view on the nature of the dielectric in protein interiors.
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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.