A simulation strategy for the atomistic modeling of flexible molecules covalently tethered to rigid surfaces: Application to peptides

David Curcó, David Zanuy, Ruth Nussinov, Carlos Alemán

Research output: Contribution to journalArticlepeer-review

Abstract

A computational strategy to model flexible molecules tethered to a rigid inert surface is presented. The strategy is able to provide uncorrelated relaxed microstructures at the atomistic level. It combines an algorithm to generate molecules tethered to the surface without atomic overlaps, a method to insert solvent molecules and ions in the simulation box, and a powerful relaxation procedure. The reliability of the strategy has been investigated by simulating two different systems: (i) mixed monolayers consisting of binary mixtures of long-chain alkyl thiols of different lengths adsorbed on a rigid inert surface and (ii) CREKA (Cys-Arg-Glu-Lys-Ala), a short linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, covalently tethered to a rigid inert surface in aqueous solution. In the first, we examined the segregation of the two species in the monolayers using different long-chain:short-chain ratios, whereas in the second, we explored the conformational space of CREKA and ions distribution considering densities of peptides per nm2 ranging from 0.03 to 1.67. Results indicate a spontaneous segregation in alkyl thiol monolayers, which enhances when the concentration of longest chains increases. However, the whole conformational profile of CREKA depends on the number of molecules tethered to the surface pointing out the large influence of molecular density on the intermolecular interactions, even though the bioactive conformation was found as the most stable in all cases.

Original languageEnglish
Pages (from-to)607-619
Number of pages13
JournalJournal of Computational Chemistry
Volume32
Issue number4
DOIs
StatePublished - Mar 2011

Keywords

  • monolayer
  • peptide
  • sampling
  • simulation
  • surface

Fingerprint

Dive into the research topics of 'A simulation strategy for the atomistic modeling of flexible molecules covalently tethered to rigid surfaces: Application to peptides'. Together they form a unique fingerprint.

Cite this