Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics

Ivan Gladich, Alex Rodriguez, Rolando P. Hong Enriquez, Filomena Guida, Federico Berti, Alessandro Laio

Research output: Contribution to journalArticle

7 Citations (Scopus)


Short peptides offer a cheap alternative to antibodies for developing sensing units in devices for concentration measurement. We here describe a computational procedure that allows designing peptides capable of binding with high affinity a target organic molecule in aqueous or nonstandard solvent environments. The algorithm is based on a stochastic search in the space of the possible sequences of the peptide, and exploits finite temperature molecular dynamics simulations in explicit solvent to check if a proposed mutation improves the binding affinity or not. The procedure automatically produces peptides which form thermally stable complexes with the target. The estimated binding free energy reaches the 13 kcal/mol for Irinotecan anticancer drug, the target considered in this work. These peptides are by construction solvent specific; namely, they recognize the target only in the solvent in which they have been designed. This feature of the algorithm calls for applications in devices in which the peptide-based sensor is required to work in denaturants or under extreme conditions of pressure and temperature.

Original languageEnglish
Pages (from-to)12963-12969
Number of pages7
JournalJournal of Physical Chemistry B
Issue number41
Publication statusPublished - 15 Oct 2015
Externally publishedYes


ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films
  • Medicine(all)

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