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Highly Efficient Computation of the Basal kon using Direct Simulation of Protein-Protein Association with Flexible Molecular Models.
- Source :
-
The journal of physical chemistry. B [J Phys Chem B] 2016 Jan 14; Vol. 120 (1), pp. 117-22. Date of Electronic Publication: 2015 Dec 30. - Publication Year :
- 2016
-
Abstract
- An essential baseline for determining the extent to which electrostatic interactions enhance the kinetics of protein-protein association is the "basal" kon, which is the rate constant for association in the absence of electrostatic interactions. However, since such association events are beyond the milliseconds time scale, it has not been practical to compute the basal kon by directly simulating the association with flexible models. Here, we computed the basal kon for barnase and barstar, two of the most rapidly associating proteins, using highly efficient, flexible molecular simulations. These simulations involved (a) pseudoatomic protein models that reproduce the molecular shapes, electrostatic, and diffusion properties of all-atom models, and (b) application of the weighted ensemble path sampling strategy, which enhanced the efficiency of generating association events by >130-fold. We also examined the extent to which the computed basal kon is affected by inclusion of intermolecular hydrodynamic interactions in the simulations.
- Subjects :
- Diffusion
Hydrodynamics
Static Electricity
Models, Molecular
Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5207
- Volume :
- 120
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The journal of physical chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 26673903
- Full Text :
- https://doi.org/10.1021/acs.jpcb.5b10747