title: Designing Short Peptides with High Affinity for Organic Molecules: A Combined Docking, Molecular Dynamics, And Monte Carlo Approach.
abstract: We present a method for designing artificial receptors capable of binding with high affinity to a chosen target organic molecule. The primary sequence of the peptide is optimized to maximize its binding affinity. Our algorithm builds on a combination of molecular dynamics, semiflexible docking, and replica exchange Monte Carlo and performs simultaneous sampling in sequence and conformational spaces carefully selecting the degree of flexibility in the mutated peptides. The approach is used to design a decapeptide able to bind efavirenz. The calculated binding energy of the designed peptide (approximately -12 kcal/mol) was confirmed experimentally by fluorescence measurements. NMR spectroscopy confirmed the interactions between the peptide and the efavirenz molecule predicted by the algorithm.
authors.affiliation: SISSA/ISAS - International School for Advanced Studies, Trieste 34100, Italy.
authors.forename: Rolando P
authors.initials: RP
authors.lastname: Hong Enriquez
authors.forename: Silvia
authors.initials: S
authors.lastname: Pavan
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tossi
authors.affiliation: T&B associati srl, Area Science Park, Padriciano 91, Trieste, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Savoini
authors.forename: Federico
authors.initials: F
authors.lastname: Berti
authors.affiliation: SISSA/ISAS - International School for Advanced Studies, Trieste 34100, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laio