The evaluation of free energy differences between specific states of a system is of fundamental interest in the study of (bio)chemical systems. Herein, we examine the use of the recently introduced confinement method (CM) to evaluate relative free energy changes upon protein/peptide mutations. CM is a path-independent technique that involves the transformation of a configurational state of the system into an ideal crystal permitting the direct computation of free energy differences. We illustrate the method by evaluating the differential stabilities between native and mutant sequences of a model peptide that has been extensively characterized by experimental approaches, the GB1 hairpin. We show a good correlation between calculated and experimental relative stabilities and discuss other possible applications of this method in the context of complex molecular conversions.

Assessment of Mutational Effects on Peptide Stability through Confinement Simulations / R. Capelli, F. Villemot, E. Moroni, G. Tiana, A. van der Vaart, G. Colombo. - In: THE JOURNAL OF PHYSICAL CHEMISTRY LETTERS. - ISSN 1948-7185. - 7:1(2016 Jan 07), pp. 126-130. [10.1021/acs.jpclett.5b02221]

Assessment of Mutational Effects on Peptide Stability through Confinement Simulations

R. Capelli
Primo
;
G. Tiana;
2016

Abstract

The evaluation of free energy differences between specific states of a system is of fundamental interest in the study of (bio)chemical systems. Herein, we examine the use of the recently introduced confinement method (CM) to evaluate relative free energy changes upon protein/peptide mutations. CM is a path-independent technique that involves the transformation of a configurational state of the system into an ideal crystal permitting the direct computation of free energy differences. We illustrate the method by evaluating the differential stabilities between native and mutant sequences of a model peptide that has been extensively characterized by experimental approaches, the GB1 hairpin. We show a good correlation between calculated and experimental relative stabilities and discuss other possible applications of this method in the context of complex molecular conversions.
free energy; molecular dynamics; protein; simulation; stability
Settore FIS/03 - Fisica della Materia
7-gen-2016
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/356032
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