dorsal/arxiv
View SchemaSimple estimation of absolute free energies for biomolecules
| Authors | F. Marty Ytreberg, Daniel M. Zuckerman |
|---|---|
| Categories | |
| ArXiv ID | physics/0508095 |
| URL | https://arxiv.org/abs/physics/0508095 |
| DOI | 10.1063/1.2174008 |
Abstract
One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is irrelevant, however, if the absolute free energy of each state can be computed. We present a method for calculating the absolute free energy that employs a simple construction of an exactly computable reference system which possesses high overlap with the state of interest. The approach requires only a physical ensemble of conformations generated via simulation, and an auxiliary calculation of approximately equal central-processing-unit (CPU) cost. Moreover, the calculations can converge to the correct free energy value even when the physical ensemble is incomplete or improperly distributed. As a "proof of principle," we use the approach to correctly predict free energies for test systems where the absolute values can be calculated exactly, and also to predict the conformational equilibrium for leucine dipeptide in implicit solvent.
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"abstract": "One reason that free energy difference calculations are notoriously difficult\nin molecular systems is due to insufficient conformational overlap, or\nsimilarity, between the two states or systems of interest. The degree of\noverlap is irrelevant, however, if the absolute free energy of each state can\nbe computed. We present a method for calculating the absolute free energy that\nemploys a simple construction of an exactly computable reference system which\npossesses high overlap with the state of interest. The approach requires only a\nphysical ensemble of conformations generated via simulation, and an auxiliary\ncalculation of approximately equal central-processing-unit (CPU) cost.\nMoreover, the calculations can converge to the correct free energy value even\nwhen the physical ensemble is incomplete or improperly distributed. As a \"proof\nof principle,\" we use the approach to correctly predict free energies for test\nsystems where the absolute values can be calculated exactly, and also to\npredict the conformational equilibrium for leucine dipeptide in implicit\nsolvent.",
"arxiv_id": "physics/0508095",
"authors": [
"F. Marty Ytreberg",
"Daniel M. Zuckerman"
],
"categories": [
"physics.bio-ph",
"physics.comp-ph"
],
"doi": "10.1063/1.2174008",
"title": "Simple estimation of absolute free energies for biomolecules",
"url": "https://arxiv.org/abs/physics/0508095"
},
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