Designing High-Affinity Peptides for Organic Molecules by Explicit Solvent Molecular Dynamics
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- 作者：Ivan Gladich ; Alex Rodriguez ; Rolando P. Hong Enriquez ; Filomena Guida ; Federico Berti ; Alessandro Laio
- 刊名：Journal of Physical Chemistry B
- 出版年：2015
- 出版时间：October 15, 2015
- 年：2015
- 卷：119
- 期：41
- 页码：12963-12969
- 全文大小：418K
- ISSN：1520-5207
文摘
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.