ArticleJournal of chemical theory and computation2013
Efficient determination of protein-protein standard binding free energies from first principles.
Article in Journal of chemical theory and computation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed.
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- Binding Free Energy Calculations Based on the Path Collective Variable along a String Pathway.The journal of physical chemistry. B · 2025Article
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- Chemically Informed Coarse-Graining of Electrostatic Forces in Charge-Rich Biomolecular Condensates.ACS central science · 2025Article
- A claudin5-binding peptide enhances the permeability of the blood-brain barrier in vitro.Science advances · 2025Article
- Structure and dynamics of the interaction of Delta and Omicron BA.1 SARS-CoV-2 variants with REGN10987 Fab reveal mechanism of antibody action.Communications biology · 2024Article
- Why is binding of a divalent metal cation to a structural motif containing four carboxylate residues not accompanied by a conformational change?Protein science : a publication of the Protein Society · 2024Article
- Advanced sampling simulations of coupled folding and binding of phage P22 N-peptide to boxB RNA.Biophysical journal · 2024Article
- Ligand Gaussian Accelerated Molecular Dynamics 3 (LiGaMD3): Improved Calculations of Binding Thermodynamics and Kinetics of Both Small Molecules and Flexible Peptides.Journal of chemical theory and computation · 2024Article
- Prebound State Discovered in the Unbinding Pathway of Fluorinated Variants of the Trypsin-BPTI Complex Using Random Acceleration Molecular Dynamics Simulations.Journal of chemical information and modeling · 2024Article
- Ligand Gaussian accelerated Molecular Dynamics 3 (LiGaMD3): Improved Calculations of Binding Thermodynamics and Kinetics of Both Small Molecules and Flexible Peptides.bioRxiv : the preprint server for biology · 2024Article
- Orientation and Membrane Partition Free Energy of PeT-Based Voltage-Sensitive Dyes from Molecular Simulations.The journal of physical chemistry. B · 2024Article
- The Diverse Nature of the Molecular Interactions That Govern the COV-2 Variants' Cell Receptor Affinity Ranking and Its Experimental Variability.International journal of molecular sciences · 2024Article
- A Rigorous Framework for Calculating Protein-Protein Binding Affinities in Membranes.Journal of chemical theory and computation · 2023Article
- Article
- The role of structural heterogeneity in the homodimerization of transmembrane proteins.The Journal of chemical physics · 2023Article
- How does the same ligand activate signaling of different receptors in TNFR superfamily: a computational study.Journal of cell communication and signaling · 2023Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
Characterizing protein-protein association quantitatively has been a longstanding challenge for computer simulations. Here, a theoretical framework is put forth that addresses this challenge on the basis of detailed all-atom molecular dynamics simulations with explicit solvent. The proposed methodology relies upon independent potential of mean force (PMF) free-energy calculations carried out sequentially, wherein the biological objects are restrained in the conformation, position and orientation of the bound state, using adequately chosen biasing potentials. These restraints systematically narrow down the configurational entropy available to the system and effectively guarantee that the relevant network of interactions is properly sampled as the two proteins reversibly associate. Decomposition of the binding process into consecutive, well-delineated stages, for both the protein complex and the individual, unbound partners, offers a rigorous definition of the standard state, from which the absolute binding free energy can be determined. The method is applied to the difficult case of the extracellular ribonuclease barnase binding to its intracellular inhibitor barstar. The calculated binding free energy is -21.0 ± 1.4 kcal/mol, which compares well with the experimental value of -19.0 ± 0.2 kcal/mol. The relatively small statistical error reflects the precision and convergence afforded by the PMF-based simulation methodology. In addition to providing an accurate reproduction of the standard binding free energy, the proposed strategy offers a detailed picture of the protein-protein interface, illuminating the thermodynamic forces that underlie reversible association. The application of the present formal framework to barnase:barstar binding provides a foundation for tackling nearly any protein-protein complex.
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