Electrostatically Embedded Molecular Tailoring Approach and Validation for Peptides

• DOI: 10.1021/ct300845q
• Publication Date: 2013-02-12T17:46:26Z
• Authors: Miho Isegawa; Bo Wang; Donald G. Truhlar
• Keywords: Fluorine; Hydrogen atom; Fragmentation

We add higher-order electronic polarization effects to the molecular tailoring approach (MTA) by embedding each fragment in background charges as combined quantum mechanical and (QM/MM) methods; resulting method considered here is called electrostatically embedded MTA (EE-MTA). compare EE-MTA for a test peptide, Ace-(Ala)20-NMe, we find that including (embedding charges) greatly improves performance. The fragmentation performed on basis of amino acids monomers, several sizes are tested. fragments capped with either hydrogen cap atoms or tuned fluorine atoms. effective core potential atom optimized so reproduce proton affinity seven types tetrapeptide, calculated shows lower mean unsigned error than obtained using atom. In application these generically show better performance compared both energy difference between an α helix β sheet (in latter case, 1.0% vs 2.7% when averaged over three two locations cut bonds). Also, accuracy charge redistribution schemes, results not particularly sensitive choices Ace-(Ala)20-NMe peptide. also illustrate dependence choice model charges, fixed depend conformation.