Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds.
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.
Senthilkumar
Kittusamy
K
Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol, UK.
Mujika
Jon I
JI
Ranaghan
Kara E
KE
Manby
Frederick R
FR
Mulholland
Adrian J
AJ
Harvey
Jeremy N
JN
D004583:Electrons; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory
Chemphyschem. 2005 Sep 5;6(9):1853-65
16086343
Dalton Trans. 2005 Nov 7;(21):3470-6
16234927
Chem Cent J. 2007 Jul 05;1:19
17880750
J Phys Chem B. 2004 May 20;108(20):6467-78
18950136
J Mol Biol. 1976 May 15;103(2):227-49
985660
J Am Chem Soc. 2004 Dec 15;126(49):16148-59
15584751
J Phys Chem B. 1998 Apr 30;102(18):3586-616
24889800
Biopolymers. 2000-2001;56(4):257-65
11754339
Chem Rev. 2005 Oct;105(10):3812-41
16218568
Chem Commun (Camb). 2005 Oct 28;(40):5068-70
16220173
J Comput Chem. 2003 Jul 30;24(10):1263-75
12820134
Chem Rev. 2003 May;103(5):1793-873
12744694
Biophys J. 2006 Feb 15;90(4):L27-9
16387767
Angew Chem Int Ed Engl. 2006 Oct 20;45(41):6856-9
16991165
Org Biomol Chem. 2004 Apr 7;2(7):968-80
15034619
Drug Discov Today. 2005 Oct 15;10(20):1393-402
16253878
J Chem Phys. 2006 Apr 28;124(16):164101
16674123
Faraday Discuss. 2004;127:165-77
15471345
J Am Chem Soc. 2005 Sep 21;127(37):12900-8
16159284
Adv Protein Chem. 2003;66:27-85
14631816
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6998-7002
12771375
Proteins. 1997 Jan;27(1):9-25
9037708
J Comput Chem. 2005 Sep;26(12):1270-8
15965971
J Chem Phys. 2005 Oct 22;123(16):164114
16268688