A Monte Carlo method for generating side chain structural ensembles
- Author(s): Bhowmick, A
- Head-Gordon, T
- et al.
Published Web Locationhttps://doi.org/10.1016/j.str.2014.10.011
© 2015 Elsevier Ltd. All rights reserved. We report a Monte Carlo side chain entropy (MC-SCE) method that uses a physical energy function inclusive of long-range electrostatics and hydrophobic potential of mean force, coupled with both backbone variations and a backbone dependent side chain rotamer library, to describe protein conformational ensembles. Using the MC-SCE method in conjunction with backbone variability, we can reliably determine the side chain rotamer populations derived from both room temperature and cryogenically cooled X-ray crystallographic structures for CypA and H-Ras and NMR J-coupling constants for CypA, Eglin-C, and the DHFR product binary complexes E:THF and E:FOL. Furthermore, we obtain near perfect discrimination between a protein's native state ensemble and ensembles of misfolded structures for 55 different proteins, thereby generating far more competitive side chain packings for all of these proteins and their misfolded states.
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