Linked Life Data

9092457

Source:http://linkedlifedata.com/resource/pubmed/id/9092457

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-4-8
pubmed:abstractText
A comparison is presented of experimentally observed hydroxyl and water hydrogens in trypsin determined from neutron density maps with the results of a 140ps molecular dynamics (MD) simulation. Experimental determination of hydrogen and deuterium atom positions in molecules as large as proteins is a unique capability of neutron diffraction. The comparison addresses the degree to which a standard force-field approach can adequately describe the local electrostatic and van der Waals forces that determine the orientations of these hydrogens. The molecular dynamics simulation, based on the all-atom AMBER force-field, allowed free rotation of all hydroxyl groups and movement of water molecules making up a bath surrounding the protein. The neutron densities, derived from 2.1A D2O-H2O difference Fourier maps, provide a database of 27 well-ordered hydroxyl hydrogens. Virtually all of the simulated hydroxyl orientations are within a standard deviation of the experimentally-observed positions, including several examples in which both the simulation and the neutron density indicate that a hydroxyl group is shifted from a 'standard' rotamer. For the most highly ordered water molecules, the hydrogen distributions calculated from the trajectory were in good agreement with neutron density; simulated water molecules that displayed multiple hydrogen bonding networks had correspondingly broadened neutron density profiles. This comparison was facilitated by development of a method to construct a pseudo 2A density map based on the hydrogen atom distributions from the simulation. The degree of internal water molecules is shown to result primarily from the electrostatic environment surrounding that water molecule as opposed to the cavity size available to the molecule. A method is presented for comparing the discrete observations sampled in a dynamics trajectory with the time-averaged data obtained from X-ray or neutron diffraction studies. This method is particularly useful for statically-disordered water molecules, in which the average location assigned from a trajectory may represent a site of relatively low occupancy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0090-5542
pubmed:author
pubmed:issnType
Print
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-87
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Hydroxyl and water molecule orientations in trypsin: comparison to molecular dynamic structures.
pubmed:affiliation
Department of Bioorganic Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
pubmed:publicationType
Journal Article, Comparative Study