The role of entropy and polarity in intermolecular contacts in protein crystals.

Department of Molecular Physiology and Biological Physics and the PSI2 Integrated Center for Structure-Function Innovation, University of Virginia, Charlottesville, VA 22908, USA.
Acta Crystallographica Section D Biological Crystallography (Impact Factor: 7.23). 06/2009; 65(Pt 5):500-9. DOI: 10.1107/S0907444909009500
Source: PubMed

ABSTRACT The integrity and X-ray diffraction quality of protein crystals depend on the three-dimensional order of relatively weak but reproducible intermolecular contacts. Despite their importance, relatively little attention has been paid to the chemical and physical nature of these contacts, which are often regarded as stochastic and thus not different from randomly selected protein surface patches. Here, logistic regression was used to analyze crystal contacts in a database of 821 unambiguously monomeric proteins with structures determined to 2.5 A resolution or better. It is shown that the propensity of a surface residue for incorporation into a crystal contact is not a linear function of its solvent-accessible surface area and that amino acids with low exposed surfaces, which are typically small and hydrophobic, have been underestimated with respect to their contact-forming potential by earlier area-based calculations. For any given solvent-exposed surface, small and hydrophobic residues are more likely to be involved in crystal contacts than large and charged amino acids. Side-chain entropy is the single physicochemical property that is most negatively correlated with the involvement of amino acids in crystal contacts. It is also shown that crystal contacts with larger buried surfaces containing eight or more amino acids have cores that are depleted of polar amino acids.

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