Bioinformatic analysis of the local dynamics of proteins and DNA

Bohdan Schneider¹, Jean-Christophe Gelly², Alexandre G. de Brevern², and

Jiří Černý¹

¹ Institute of Biotechnology AS CR, Vídeňská 1083, CZ-142 20 Prague, Czech Republic

² University Paris Diderot, Sorbonne Paris Cité, UMR_S 1134, F-75739 Paris, France

Dynamics of proteins and nucleic acids is as important as their averaged molecular structures. Diffraction images contain information about the local molecular dynamics that is concealed in so-called B-factors (officially temperature displacement factors). To find out how well the crystal-derived B-factors represent the dynamic behavior of atoms and residues of key biomolecules, proteins and DNA, we analyzed distributions of scaled B-factors in a well-curated non-redundant dataset of almost a thousand protein/DNA complexes that has been described in Schneider et al. Nucleic Acids Research, 42 (2014). The analysis confirmed several expected features of protein and DNA dynamics but it also revealed some surprising facts. Solvent-accessible amino acids have B-factors larger than residues forming the interface with another protein or DNA molecule and the core-forming amino acids have B-factors the lowest so that their movement is very restricted. Really unique feature distinguishing the core-forming amino acids from any other type of amino acid residue is the fact that their side chains are restricted in their movements more than the main chains. The protein core is therefore extremely well packed leaving minimum free space for atomic movements. Surprising are low values of B-factors of the water molecules bridging protein and DNA that are actually significantly lower than the B-factors of DNA phosphates. Solvent-accessible phosphates are extremely flexible; they and DNA bases stiffen significantly upon complexation with proteins but overall are more flexible than amino acids. Unexpected and perhaps to some extent worrisome is also the fact that the features discriminating different types of residues quickly vanish in structures with lower crystallographic resolution. Some of the observed trends are a likely consequence of improper refinement protocols that may need rectifying.

Acknowledgments. This study was supported by BIOCEV CZ.1.05/1.1.00/02.0109 from the ERDF and by grant P305/12/1801 from the Czech Science Foundation.