Development of polarizable models for molecular mechanical calculations II: Induced dipole models significantly improve accuracy of intermolecular interaction energies

Junmei Wang, Piotr Cieplak, Jie Li, Jun Wang, Qin Cai, Mengjuei Hsieh, Hongxing Lei, Ray Luo, Yong Duan

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

In the companion paper, we presented a set of induced dipole interaction models using four types of screening functions, which include the Applequist (no screening), the Thole linear, the Thole exponential model, and the Thole Tinker-like (another form of exponential screening function) functions. In this work, we evaluate the performance of polarizability models using a large set of amino acid analog pairs in conformations that are frequently observed in protein structures as a benchmark. For each amino acid pair, we calculated quantum mechanical interaction energies at the MP2/aug-cc-pVTZ//MP2/6-311++G(d,p) level with the basis set superposition error (BSSE) correction and compared them with molecular mechanics results. Encouragingly, all polarizable models significantly outperform the additive F94 and F03 models (mimicking AMBER ff94/ff99 and ff03 force fields, respectively) in reproducing the BSSE-corrected quantum mechanical interaction energies. In particular, the root-mean-square errors (RMSEs) for three Thole models in Set A (where the 1-2 and 1-3 interactions are turned off and all 1-4 interactions are included) are 1.456, 1.417, and 1.406 kcal/mol for model AL (Thole Linear), model AE (Thole exponential), and model AT (Thole Tinker-like), respectively. In contrast, the RMSEs are 3.729 and 3.433 kcal/mol for F94 and F03 models, respectively. A similar trend was observed for the average unsigned errors (AUEs), which are 1.057, 1.025, 1.011, 2.219, and 2.070 kcal/mol for AL, AE, AT, F94/ff99, and F03, respectively. Analyses based on the trend line slopes indicate that the two fixed charge models substantially underestimate the relative strengths of noncharge-charge interactions by 24 (F03) and 35% (F94), respectively, whereas the four polarizable models overestimate the relative strengths by 5 (AT), 3 (AL, AE), and 13% (AA), respectively. Agreement was further improved by adjusting the van der Waals parameters. Judging from the notably improved accuracy in comparison with the fixed charge models, the polarizable models are expected to form the foundation for the development of high quality polarizable force fields for protein and nucleic acid simulations.

Original languageEnglish (US)
Pages (from-to)3100-3111
Number of pages12
JournalJournal of Physical Chemistry B
Volume115
Issue number12
DOIs
StatePublished - Mar 31 2011

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

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