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Methods for Calculating the Absolute Entropy and free energy of biological systems based on ideas from Polymer Physics
| Content Provider | PubMed Central |
|---|---|
| Author | Hagai, Meirovitch |
| Abstract | The commonly used simulation techniques, Metropolis Monte Carlo (MC) and molecular dynamics (MD) are of a dynamical type which enables one to sample system configurations i correctly with the Boltzmann probability, Pi B while the value of Pi B is not provided directly; therefore, it is difficult to obtain the absolute entropy, S ~ -ln Pi B, and the Helmholtz free energy, F. With a different simulation approach developed in polymer physics, a chain is grown step-by-step with transition probabilities (TPs), and thus their product is the value of the construction probability; therefore, the entropy is known. Because all exact simulation methods are equivalent, i.e. they lead to the same averages and fluctuations of physical properties, one can treat an MC or MD sample as if its members have rather been generated step-by-step. Thus, each configuration i of the sample can be reconstructed (from nothing) by calculating the TPs with which it could have been constructed. This idea applies also to bulk systems such as fluids or magnets. This approach has led earlier to the “local states” (LS) and the “hypothetical scanning” (HS) methods, which are approximate in nature. A recent development is the hypothetical scanning Monte Carlo (HSMC) (or molecular dynamics, HSMD) method which is based on stochastic TPs where all interactions are taken into account. In this respect HSMC(D) can be viewed as exact and the only approximation involved is due to insufficient MC(MD) sampling for calculating the TPs. The validity of HSMC has been established by applying it first to liquid argon, TIP3P water, self-avoiding walks, and polyglycine models, where the results for F were found to agree with those obtained by other methods. Subsequently, HSMD was applied to mobile loops of the enzymes porcine pancreatic α-amylase and acetylcholineesterase in explicit water, where the difference of F between the bound and free states of the loop was calculated. Currently HSMD is being extended for calculating the absolute and relative free energy of ligand-enzyme binding. We describe the whole approach and discuss future directions. |
| Related Links | http://dx.doi.org/10.1002/jmr.973 |
| Page Count | 1 |
| Starting Page | 153 |
| File Format | |
| ISSN | 09523499 |
| e-ISSN | 10991352 |
| Journal | Journal of molecular recognition : JMR |
| Issue Number | 2 |
| Volume Number | 23 |
| Language | English |
| Publisher Date | 2009-01-01 |
| Access Restriction | Open |
| Subject Keyword | Molecular Biology Structural Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Structural Biology Molecular Biology |
