Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their identity, properties and binding capabilities. In order to shed light on the energetic side of interactions of amino acids between themselves and with deoxyribonucleotides, we present the Amino Acid Interaction web server (http://bioinfo.uochb.cas.cz/INTAA/). INTAA offers the calculation of the residue Interaction Energy Matrix for any protein structure (deposited in Protein Data Bank or submitted by the user) and a comprehensive analysis of the interfaces in protein-DNA complexes. The Interaction Energy Matrix web application aims to identify key residues within protein structures which contribute significantly to the stability of the protein. The application provides an interactive user interface enhanced by 3D structure viewer for efficient visualization of pairwise and net interaction energies of individual amino acids, side chains and backbones. The protein-DNA interaction analysis part of the web server allows the user to view the relative abundance of various configurations of amino acid-deoxyribonucleotide pairs found at the protein-DNA interface and the interaction energies corresponding to these configurations calculated using a molecular mechanical force field. The effects of the sugar-phosphate moiety and of the dielectric properties of the solvent on the interaction energies can be studied for the various configurations.

• MeSH
• Amino Acids chemistry   MeSH
• DNA-Binding Proteins chemistry   MeSH
• DNA chemistry   MeSH
• Internet MeSH
• Nucleotides chemistry   MeSH
• Software * MeSH
• Protein Stability MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amino Acids MeSH
• DNA-Binding Proteins MeSH
• DNA MeSH
• Nucleotides MeSH

Decades of intensive experimental studies of the recognition of DNA sequences by proteins have provided us with a view of a diverse and complicated world in which few to no features are shared between individual DNA-binding protein families. The originally conceived direct readout of DNA residue sequences by amino acid side chains offers very limited capacity for sequence recognition, while the effects of the dynamic properties of the interacting partners remain difficult to quantify and almost impossible to generalise. In this work we investigated the energetic characteristics of all DNA residue-amino acid side chain combinations in the conformations found at the interaction interface in a very large set of protein-DNA complexes by the means of empirical potential-based calculations. General specificity-defining criteria were derived and utilised to look beyond the binding motifs considered in previous studies. Linking energetic favourability to the observed geometrical preferences, our approach reveals several additional amino acid motifs which can distinguish between individual DNA bases. Our results remained valid in environments with various dielectric properties.

• MeSH
• Adenine chemistry   metabolism   MeSH
• Amino Acid Motifs * MeSH
• Amino Acids chemistry   metabolism   MeSH
• Cytosine chemistry   metabolism   MeSH
• Databases, Protein MeSH
• DNA-Binding Proteins chemistry   genetics   metabolism   MeSH
• DNA chemistry   genetics   metabolism   MeSH
• Guanine chemistry   metabolism   MeSH
• Nucleic Acid Conformation MeSH
• Crystallography, X-Ray MeSH
• Models, Molecular MeSH
• Statistics as Topic methods   MeSH
• Protein Structure, Tertiary MeSH
• Thermodynamics MeSH
• Thymine chemistry   metabolism   MeSH
• Protein Binding MeSH
• Binding Sites genetics   MeSH
• Computational Biology methods   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adenine MeSH
• Amino Acids MeSH
• Cytosine MeSH
• DNA-Binding Proteins MeSH
• DNA MeSH
• Guanine MeSH
• Thymine MeSH

We evaluate the performance of the most widely used wavefunction, density functional theory, and semiempirical methods for the description of noncovalent interactions in a set of larger, mostly dispersion-stabilized noncovalent complexes (the L7 data set). The methods tested include MP2, MP3, SCS-MP2, SCS(MI)-MP2, MP2.5, MP2.X, MP2C, DFT-D, DFT-D3 (B3-LYP-D3, B-LYP-D3, TPSS-D3, PW6B95-D3, M06-2X-D3) and M06-2X, and semiempirical methods augmented with dispersion and hydrogen bonding corrections: SCC-DFTB-D, PM6-D, PM6-DH2 and PM6-D3H4. The test complexes are the octadecane dimer, the guanine trimer, the circumcoronene…adenine dimer, the coronene dimer, the guanine-cytosine dimer, the circumcoronene…guanine-cytosine dimer, and an amyloid fragment trimer containing phenylalanine residues. The best performing method is MP2.5 with relative root mean square deviation (rRMSD) of 4 %. It can thus be recommended as an alternative to the CCSD(T)/CBS (alternatively QCISD(T)/CBS) benchmark for molecular systems which exceed current computational capacity. The second best non-DFT method is MP2C with rRMSD of 8 %. A method with the most favorable "accuracy/cost" ratio belongs to the DFT family: BLYP-D3, with an rRMSD of 8 %. Semiempirical methods deliver less accurate results (the rRMSD exceeds 25 %). Nevertheless, their absolute errors are close to some much more expensive methods such as M06-2X, MP2 or SCS(MI)-MP2, and thus their price/performance ratio is excellent.

• Publication type
• Journal Article MeSH