title: Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds.
abstract: Combined quantum mechanics/molecular mechanics (QM/MM) methods are increasingly important for the study of chemical reactions and systems in condensed phases. Here, we have tested the accuracy of a density functional theory-based QM/MM implementation (B3LYP/6-311+G(d,p)/CHARMM27) on a set of biologically relevant interactions by comparison with full QM calculations. Intermolecular charge transfer due to hydrogen bond formation is studied to assess the severity of spurious polarization of QM atoms by MM point charges close to the QM/MM boundary. The changes in total electron density and natural bond orbital atomic charges due to hydrogen bond formation in selected complexes obtained at the QM/MM level are compared with full QM results. It is found that charge leakage from the QM atoms to MM atomic point charges close to the QM/MM boundary is not a serious problem, at least with limited basis sets. The results are encouraging in showing that important properties of key biomolecular interactions can be treated well at the QM/MM level employing good-quality levels of QM theory.
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol, UK.
authors.forename: Kittusamy
authors.initials: K
authors.lastname: Senthilkumar
authors.forename: Jon I
authors.initials: JI
authors.lastname: Mujika
authors.forename: Kara E
authors.initials: KE
authors.lastname: Ranaghan
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Manby
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Harvey
mesh_terms: D004583:Electrons; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory
references.citation: Chemphyschem. 2005 Sep 5;6(9):1853-65
references.pmid: 16086343
references.citation: Dalton Trans. 2005 Nov 7;(21):3470-6
references.pmid: 16234927
references.citation: Chem Cent J. 2007 Jul 05;1:19
references.pmid: 17880750
references.citation: J Phys Chem B. 2004 May 20;108(20):6467-78
references.pmid: 18950136
references.citation: J Mol Biol. 1976 May 15;103(2):227-49
references.pmid: 985660
references.citation: J Am Chem Soc. 2004 Dec 15;126(49):16148-59
references.pmid: 15584751
references.citation: J Phys Chem B. 1998 Apr 30;102(18):3586-616
references.pmid: 24889800
references.citation: Biopolymers. 2000-2001;56(4):257-65
references.pmid: 11754339
references.citation: Chem Rev. 2005 Oct;105(10):3812-41
references.pmid: 16218568
references.citation: Chem Commun (Camb). 2005 Oct 28;(40):5068-70
references.pmid: 16220173
references.citation: J Comput Chem. 2003 Jul 30;24(10):1263-75
references.pmid: 12820134
references.citation: Chem Rev. 2003 May;103(5):1793-873
references.pmid: 12744694
references.citation: Biophys J. 2006 Feb 15;90(4):L27-9
references.pmid: 16387767
references.citation: Angew Chem Int Ed Engl. 2006 Oct 20;45(41):6856-9
references.pmid: 16991165
references.citation: Org Biomol Chem. 2004 Apr 7;2(7):968-80
references.pmid: 15034619
references.citation: Drug Discov Today. 2005 Oct 15;10(20):1393-402
references.pmid: 16253878
references.citation: J Chem Phys. 2006 Apr 28;124(16):164101
references.pmid: 16674123
references.citation: Faraday Discuss. 2004;127:165-77
references.pmid: 15471345
references.citation: J Am Chem Soc. 2005 Sep 21;127(37):12900-8
references.pmid: 16159284
references.citation: Adv Protein Chem. 2003;66:27-85
references.pmid: 14631816
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6998-7002
references.pmid: 12771375
references.citation: Proteins. 1997 Jan;27(1):9-25
references.pmid: 9037708
references.citation: J Comput Chem. 2005 Sep;26(12):1270-8
references.pmid: 15965971
references.citation: J Chem Phys. 2005 Oct 22;123(16):164114
references.pmid: 16268688