Performance of various density functionals for the hydrogen bonds in DNA base pairs Tushar van der Wijst a,b , Ce ´lia Fonseca Guerra b , Marcel Swart b,c,d , F. Matthias Bickelhaupt b, * a Fachbereich Chemie, Lehrstuhl fu ¨ r Anorganische Chemie III, Universita ¨ t Dortmund, Otto-Hahn-Straße 6, D-44227 Dortmund, Germany b Theoretische Chemie, Scheikundig Laboratorium der Vrije Universiteit, De Boelelaan 1083, NL-1081 HV Amsterdam, The Netherlands c Institucio ´ Catalana de Recerca i Estudis Avanc ¸ats (ICREA), E-08010 Barcelona, Catalonia, Spain d Institut de Quı ´mica Computacional, Universitat de Girona, Campus Montilivi, E-17071 Girona, Catalonia, Spain Received 8 June 2006; in final form 16 June 2006 Available online 23 June 2006 Abstract We have investigated the performance of seven popular density functionals (B3LYP, BLYP, BP86, mPW, OPBE, PBE, PW91) for describing the geometry and stability of the hydrogen bonds in DNA base pairs. For the gas-phase situation, the hydrogen-bond lengths and strengths in the DNA pairs have been compared to the best ab initio results available in the literature (MP2). For a comparison with the crystallographic experiments, the first crystal-environment shell was taken into account in our DNA model systems. BP86 and PW91 excellently recover both the ab initio and experimental values. B3LYP consistently underestimates hydrogen-bond strengths and over- estimates hydrogen-bond distances. Ó 2006 Elsevier B.V. All rights reserved. 1. Introduction Hydrogen bonds are important in many fields of biolog- ical chemistry. They play, for instance, a key role in the working of the genetic code. In DNA, the two helical chains of nucleotides are held together by the hydrogen bonds that occur in a selective fashion between a purine and a pyrimidine nucleic base giving rise to the Watson– Crick pairs adenine–thymine (AT) and guanine–cytosine (GC), see Fig. 1. These hydrogen bonds in DNA have been the subject of many theoretical investigations. The incapacity of the ab initio Hartree–Fock method to describe these hydrogen bonds in DNA, on one hand, and the extreme computa- tional cost of ab initio MP2 or coupled-cluster methods for systems of this size, on the other hand, make density functional theory (DFT) an excellent alternative which combines accuracy and computational efficiency. One of the most widely used functionals, B3LYP, has also been applied to the DNA base pairs. B3LYP is generally consid- ered to be a reliable general-purpose alternative to MP2 that is to be preferred over other DFT approaches. How- ever, it was recently shown that B3LYP does not in general outperform all other functionals regarding the computa- tion of chemical reaction barriers [1–6]. Often, it performs even less accurately than popular GGA-based functionals (e.g., OLYP and also BLYP), and in certain cases B3LYP even fails to reproduce the barrier [1–6]. Another peculiar phenomenon was observed by Bertran et al. [7] in a study on DNA base pairs in the gas phase: the agree- ment for the hydrogen bonds in the DNA base pair AT with crystallographic data [8,9] was excellent, however for the other base pair GC it failed to reproduce the crystallo- graphic data. 0009-2614/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.cplett.2006.06.057 * Corresponding author. Fax: +31 20 598 7629. E-mail address: FM.Bickelhaupt@few.vu.nl (F.M. Bickelhaupt). www.elsevier.com/locate/cplett Chemical Physics Letters 426 (2006) 415–421