title: Assessment of Mutational Effects on Peptide Stability through Confinement Simulations.
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.
authors.affiliation: Dipartimento di Fisica, Università degli Studi di Milano and INFN , via Celoria 16, 20133 Milan, Italy.|Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche , via Mario Bianco 9, 20131 Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Capelli
authors.affiliation: Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
authors.forename: François
authors.initials: F
authors.lastname: Villemot
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche , via Mario Bianco 9, 20131 Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moroni
authors.affiliation: Dipartimento di Fisica, Università degli Studi di Milano and INFN , via Celoria 16, 20133 Milan, Italy.|Center for Complexity and Biosystems and Department of Physics, Università degli Studi di Milano and INFN , via Celoria 16, 20133 Milan, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Tiana
authors.affiliation: Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
authors.forename: Arjan
authors.initials: A
authors.lastname: van der Vaart
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche , via Mario Bianco 9, 20131 Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
mesh_terms: D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000235:genetics*; D055550:Protein Stability; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D050505:Mutant Proteins; D010455:Peptides
keywords: free energy; molecular dynamics; protein; simulation; stability