title: Quantifying the intrinsic effects of two point mutation models of proline-proline diamino acid diamide: a first-principle computational study.
abstract: Two sites of a Pro-Pro diamide were subjected to individual Pro --> Thr point mutations. The parent diamide Pro-Pro as well as selected conformers of the Pro-Thr and Thr-Pro mutant models were subjected to molecular computations at the B3LYP/6-31G(d) level of theory. At the optimized geometries, thermodynamic functions (S, H, and G) were computed. In order to assess relative stabilities of the mutant models, isodesmic reactions were constructed to calculate DeltaS, DeltaH, and DeltaG, relative to the initial Pro-Pro state. The importance of intramolecular hydrogen bonds, involving the -OH group of the Thr side chain, which emerged after the point mutations were also examined. Our findings suggest a novel approach to analyzing the stability of point mutants in peptide models through the analysis of thermodynamic functions.
authors.affiliation: Ontario Cancer Institute, Division of Cancer Genomics and Proteomics, MaRS Center, Toronto Medical Discovery Tower, 101 College Street, Room 5-359, Toronto, Ontario, M5G 1L7, Canada. michelle.sahai@utoronto.ca
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Sahai
authors.forename: Bela
authors.initials: B
authors.lastname: Viskolcz
authors.forename: Emil F
authors.initials: EF
authors.lastname: Pai
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
mesh_terms: D019295:Computational Biology; D003958:Diamide / Q000031:analogs & derivatives* / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry / Q000235:genetics*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008957:Models, Genetic; D017354:Point Mutation; D011487:Protein Conformation; D013816:Thermodynamics; D013912:Threonine / Q000235:genetics