Computational mapping identifies the binding sites of organic solvents on proteins

Sheldon Dennis, T. Körtvélyesi, Sandor Vajda

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Computational mapping places molecular probes - Small molecules or functional groups - On a protein surface to identify the most favorable binding positions. Although x-ray crystallography and NMR show that organic solvents bind to a limited number of sites on a protein, current mapping methods result in hundreds of energy minima and do not reveal why some sites bind molecules with different sizes and polarities. We describe a mapping algorithm that explains the origin of this phenomenon. The algorithm has been applied to hen egg-white lysozyme and to thermolysin, interacting with eight and four different ligands, respectively. In both cases the search finds the consensus site to which all molecules bind, whereas other positions that bind only certain ligands are not necessarily found. The consensus sites are pockets of the active site, lined with partially exposed hydrophobic residues and with a number of polar residues toward the edge. These sites can accommodate each ligand in a number of rotational states, some with a hydrogen bond to one of the nearby donor/acceptor groups. Specific substrates and/or inhibitors of hen egg-white lysozyme and thermolysin interact with the same side chains identified by the mapping, but form several hydrogen bonds and bind in unique orientations.

Original languageEnglish
Pages (from-to)4290-4295
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number7
DOIs
Publication statusPublished - Apr 2 2002

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Thermolysin
Egg White
Binding Sites
Ligands
Hydrogen
Molecular Probes
Crystallography
Proteins
Catalytic Domain
Membrane Proteins
X-Rays
hen egg lysozyme

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Computational mapping identifies the binding sites of organic solvents on proteins. / Dennis, Sheldon; Körtvélyesi, T.; Vajda, Sandor.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 7, 02.04.2002, p. 4290-4295.

Research output: Contribution to journalArticle

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