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)

Abstract

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
Volume119
Issue number41
DOIs
Publication statusPublished - 15 Oct 2015
Externally publishedYes

Fingerprint

Molecular Dynamics Simulation
Peptides
peptides
affinity
Molecular dynamics
molecular dynamics
Molecules
molecules
irinotecan
Equipment and Supplies
Temperature
mutations
antibodies
Antibodies
Free energy
drugs
free energy
Pressure
Mutation
temperature

ASJC Scopus subject areas

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

Cite this

Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics. / Gladich, Ivan; Rodriguez, Alex; Hong Enriquez, Rolando P.; Guida, Filomena; Berti, Federico; Laio, Alessandro.

In: Journal of Physical Chemistry B, Vol. 119, No. 41, 15.10.2015, p. 12963-12969.

Research output: Contribution to journalArticle

Gladich, Ivan ; Rodriguez, Alex ; Hong Enriquez, Rolando P. ; Guida, Filomena ; Berti, Federico ; Laio, Alessandro. / Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics. In: Journal of Physical Chemistry B. 2015 ; Vol. 119, No. 41. pp. 12963-12969.
@article{e9e61c10fb5c456cba22046b03690571,
title = "Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics",
abstract = "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.",
author = "Ivan Gladich and Alex Rodriguez and {Hong Enriquez}, {Rolando P.} and Filomena Guida and Federico Berti and Alessandro Laio",
year = "2015",
month = "10",
day = "15",
doi = "10.1021/acs.jpcb.5b06227",
language = "English",
volume = "119",
pages = "12963--12969",
journal = "Journal of Physical Chemistry B Materials",
issn = "1520-6106",
publisher = "American Chemical Society",
number = "41",

}

TY - JOUR

T1 - Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics

AU - Gladich, Ivan

AU - Rodriguez, Alex

AU - Hong Enriquez, Rolando P.

AU - Guida, Filomena

AU - Berti, Federico

AU - Laio, Alessandro

PY - 2015/10/15

Y1 - 2015/10/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84944339270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944339270&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.5b06227

DO - 10.1021/acs.jpcb.5b06227

M3 - Article

VL - 119

SP - 12963

EP - 12969

JO - Journal of Physical Chemistry B Materials

JF - Journal of Physical Chemistry B Materials

SN - 1520-6106

IS - 41

ER -