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Assessment of enveloping distribution sampling to calculate relative free enthalpies of binding for eight netropsin-DNA duplex complexes in aqueous solution
- Source :
- Journal of Computational Chemistry
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- The performance of enveloping distribution sampling (EDS) simulations to estimate free enthalpy differences associated with seven alchemical transformations of A-T into G-C base pairs at the netropsin binding site in the minor groove of a 13-base pair DNA duplex in aqueous solution is evaluated. It is demonstrated that sufficient sampling can be achieved with a two-state EDS Hamiltonian even for large perturbations such as the simultaneous transformation of up to three A-T into three G-C base pairs. The two parameters required to define the EDS reference state Hamiltonian are obtained automatically using a modified version of a scheme presented in earlier work. The sensitivity of the configurational sampling to a variation of these parameters is investigated in detail. Although for relatively small perturbations, that is, one base pair, the free enthalpy estimate depends only weakly on the EDS parameters, the sensitivity is stronger for the largest perturbation. Yet, EDS offers various convenient measures to evaluate the degree of sampling and thus the reliability of the free enthalpy estimate and appears to be an efficient alternative to the conventional thermodynamic integration methodology to obtain free energy differences for molecular systems.
- Subjects :
- Dna duplex
Base pair
Thermodynamics
Thermodynamic integration
Perturbation (astronomy)
010402 general chemistry
01 natural sciences
chemistry.chemical_compound
symbols.namesake
Molecular recognition
0103 physical sciences
Computer Simulation
Aqueous solution
Molecular Structure
010304 chemical physics
Water
Netropsin
DNA
General Chemistry
0104 chemical sciences
Gibbs free energy
Computational Mathematics
chemistry
symbols
Physical chemistry
Subjects
Details
- ISSN :
- 01928651
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Journal of Computational Chemistry
- Accession number :
- edsair.doi.dedup.....51492345f9f632ff763abd52e577964d