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.
authors.affiliation: International School for Advanced Studies (SISSA) , Via Bonomea 265, I-34136 Trieste, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gladich
authors.affiliation: International School for Advanced Studies (SISSA) , Via Bonomea 265, I-34136 Trieste, Italy.
authors.forename: Alex
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Istituto Italiano di Tecnologia (IIT) , Genova, Italy.
authors.forename: Rolando P
authors.initials: RP
authors.lastname: Hong Enriquez
authors.affiliation: International School for Advanced Studies (SISSA) , Via Bonomea 265, I-34136 Trieste, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Guida
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, University of Trieste , I-34136 Trieste, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Berti
authors.affiliation: International School for Advanced Studies (SISSA) , Via Bonomea 265, I-34136 Trieste, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laio
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D009930:Organic Chemicals / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D009930:Organic Chemicals; D010455:Peptides; D012997:Solvents