Assessing the Performance of MM/PBSA, MM/GBSA, and QM-MM/GBSA Approaches on Protein/Carbohydrate Complexes: Effect of Implicit Solvent Models, QM Methods, and Entropic Contributions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00106636" target="_blank" >RIV/00216224:14740/18:00106636 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/acs.jpcb.8b03655" target="_blank" >http://dx.doi.org/10.1021/acs.jpcb.8b03655</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jpcb.8b03655" target="_blank" >10.1021/acs.jpcb.8b03655</a>
Alternative languages
Result language
angličtina
Original language name
Assessing the Performance of MM/PBSA, MM/GBSA, and QM-MM/GBSA Approaches on Protein/Carbohydrate Complexes: Effect of Implicit Solvent Models, QM Methods, and Entropic Contributions
Original language description
Rapid and accurate binding affinity prediction of protein-carbohydrate complexes is a major challenge in glycomimetics design. Among the existing computational techniques, endpoint methods have received considerable interest because of their low computational cost. However, significant obstacles remain when such methods are applied to protein-glycan complexes. This article reports the performance of end-point free-energy calculation methods: molecular mechanics/Poisson-Boltzmann surface area (MM/ PBSA), MM/generalized Born surface area (MM/GBSA), and quantum mechanics-MM/GBSA (QM-MM/GBSA) on monosaccharides bound to RSL lectin from Ralstonia solanacearum. A careful investigation of the molecular dynamics simulation length, van der Waals radii sets, GB models, QM Hamiltonians, and entropic compensation has been made, and the results are compared with the experimental binding free energies from isothermal titration calorimetry/surface plasmon resonance measurements. The binding free energies using implicit solvent methods are found to be sensitive to the simulation length, radii set, GB model, and QM Hamiltonian. A simulation length of 10 ns using the radii set mbondi provides the best agreement with the experimental values (r(2) = 0.96) by MM/PBSA. The GB(HCT) model is in accord with the experimental values in MM/GBSA (r(2) = 0.91) or in combination with parameterized model number 6 (PM6) (r(2) = 0.98) in QM-MM/GBSA. Out of 12 QM Hamiltonians tested, PM6, density functional theory-based tight binding (DFTB), and their variants proved to be more efficient than other semiempirical methods. These methods perform equally well in predicting both absolute and relative binding free energies.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Physical Chemistry B
ISSN
1520-6106
e-ISSN
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Volume of the periodical
122
Issue of the periodical within the volume
34
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
8113-8121
UT code for WoS article
000443922600001
EID of the result in the Scopus database
2-s2.0-85052751582