title: Representative Amino Acid Side-Chain Interactions in Protein-DNA Complexes: A Comparison of Highly Accurate Correlated Ab Initio Quantum Mechanical Calculations and Efficient Approaches for Applications to Large Systems.
abstract: Representative pairs of amino acid side chains and nucleic acid bases extracted from available high-quality structures of protein-DNA complexes were analyzed using a range of computational methods. CCSD(T)/CBS interaction energies were calculated for the chosen 272 pairs. These reference interaction energies were used to test the MP2.5/CBS, MP2.X/CBS, MP2-F12, DFT-D3, PM6, and Amber force field methods. Method MP2.5 provided excellent agreement with reference data (root-mean-square error (RMSE) of 0.11 kcal/mol), which is more than 1 order of magnitude faster than the CCSD(T) method. When MP2-F12 and MP2.5 were combined, the results were within reasonable accuracy (0.20 kcal/mol), with a computational savings of almost 2 orders of magnitude. Therefore, this method is a promising tool for accurate calculations of interaction energies in protein-DNA motifs of up to ∼100 atoms, for which CCSD(T)/CBS benchmark calculations are not feasible. B3-LYP-D3 calculated with def2-TZVPP and def2-QZVP basis sets yielded sufficiently good results with a reasonably small RMSE. This method provided better results for neutral systems, whereas positively charged species exhibited the worst agreement with the benchmark data. The Amber force field yielded unbalanced results-performing well for systems containing nonpolar amino acids but severely underestimating interaction energies for charged complexes. The semiempirical PM6 method with corrections for hydrogen bonding and dispersion energy (PM6-D3H4) exhibited considerably smaller error than the Amber force field, which makes it an effective tool for modeling extended protein-ligand complexes (of up to 10,000 atoms).
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague, Czech Republic.|Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in Prague , Albertov 6, 128 43 Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Hostaš
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague, Czech Republic.|Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in Prague , Albertov 6, 128 43 Prague, Czech Republic.
authors.forename: Dávid
authors.initials: D
authors.lastname: Jakubec
authors.affiliation: EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Laskowski
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague, Czech Republic.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Gnanasekaran
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Řezáč
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vondrášek
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague, Czech Republic.|Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Palacký University , 771 46 Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hobza
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D000596:Amino Acids; D011506:Proteins; D004247:DNA