Algorithms for computational solvent mapping of proteins

Tamas Kortvelyesi, Sheldon Dennis, Michael Silberstein, Lawrence Brown, Sandor Vajda

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Computational mapping methods place molecular probes (small molecules or functional groups) on a protein surface to identify the most favorable binding positions by calculating an interaction potential. We have developed a novel computational mapping program called CS-Map (computational solvent mapping of proteins), which differs from earlier mapping methods in three respects: (i) it initially moves the ligands on the protein surface toward regions with favorable electrostatics and desolvation, (ii) the final scoring potential accounts for desolvation, and (iii) the docked ligand positions are clustered, and the clusters are ranked on the basis of their average free energies. To understand the relative importance of these factors, we developed alternative algorithms that use the DOCK and GRAMM programs for the initial search. Because of the availability of experimental solvent mapping data, lysozyme and thermolysin are considered as test proteins. Both DOCK and GRAMM speed up the initial search, and the combined algorithms yield acceptable mapping results. However, the DOCK-based approaches place the consensus site farther from its experimentally determined position than CS-Map, primarily because of the lack of a solvation term in the initial search. The GRAMM-based program also finds the correct consensus site for thermolysin. We conclude that good sampling is the most important requirement for successful mapping, but accounting for desolvation and clustering of ligand positions also help to reduce the number of false positives.

Original languageEnglish
Pages (from-to)340-351
Number of pages12
JournalProteins: Structure, Function and Genetics
Volume51
Issue number3
DOIs
Publication statusPublished - May 15 2003

Keywords

  • Clustering
  • Docking
  • Enzyme active site
  • Ligand binding
  • Scoring
  • Solvation

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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