Probing the Relation Between Community Evolution in Dynamic Residue Interaction Networks and Xylanase Thermostability

Residue-residue interactions are the basis of protein thermostability. The molecular conformations of <italic>Streptomyces lividans</italic> xylanase (xyna_strli) and <italic>Thermoascus aurantiacus</italic> xylanase (xyna_theau) at 300K, 325K and 350K were obtained by Molecular Dynamics (MD) simulations. Dynamic weighted residue interaction networks were constructed and the rigid-communities were detected using the ESPRA algorithm and the Evolving Graph+Fast-Newman algorithm. The residues in the rigid-communities are primarily located in loop2, short helixes <inline-formula><tex-math notation="LaTeX">$\alpha 2^{\prime}, \alpha 3^{\prime}, \alpha 4^{\prime}$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:msup><mml:mn>2</mml:mn><mml:mo>'</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mi>α</mml:mi><mml:msup><mml:mn>3</mml:mn><mml:mo>'</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mi>α</mml:mi><mml:msup><mml:mn>4</mml:mn><mml:mo>'</mml:mo></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq1-2922906.gif"/></alternatives></inline-formula> and helixes <inline-formula><tex-math notation="LaTeX">$\alpha 3$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:mn>3</mml:mn></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq2-2922906.gif"/></alternatives></inline-formula> and <inline-formula><tex-math notation="LaTeX">$\alpha 4$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq3-2922906.gif"/></alternatives></inline-formula>. Thus, the rigid-community is close to the N-terminus of xylanase, which is usually stabilized to increase thermostability using site-directed mutagenesis. The evolution of the rigid-community with increasing temperature shows a stable synergistic interaction between loop2, <inline-formula><tex-math notation="LaTeX">$\alpha 2^{\prime}, \alpha 3^{\prime}$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:msup><mml:mn>2</mml:mn><mml:mo>'</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mi>α</mml:mi><mml:msup><mml:mn>3</mml:mn><mml:mo>'</mml:mo></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq4-2922906.gif"/></alternatives></inline-formula> and <inline-formula><tex-math notation="LaTeX">$\alpha 4^{\prime}$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:msup><mml:mn>4</mml:mn><mml:mo>'</mml:mo></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq5-2922906.gif"/></alternatives></inline-formula> in xyna_theau. In particular, the short helixes <inline-formula><tex-math notation="LaTeX">$\alpha 2^{\prime}$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:msup><mml:mn>2</mml:mn><mml:mo>'</mml:mo></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq6-2922906.gif"/></alternatives></inline-formula> and <inline-formula><tex-math notation="LaTeX">$\alpha 3^{\prime}$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:msup><mml:mn>3</mml:mn><mml:mo>'</mml:mo></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq7-2922906.gif"/></alternatives></inline-formula> form a “thermo helix” to promote thermostability. In addition, tight global interactions between loop2, <inline-formula><tex-math notation="LaTeX">$\alpha 2^{\prime}, \alpha 3^{\prime}, \alpha 3, \alpha 4^{\prime}$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:msup><mml:mn>2</mml:mn><mml:mo>'</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mi>α</mml:mi><mml:msup><mml:mn>3</mml:mn><mml:mo>'</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mi>α</mml:mi><mml:mn>3</mml:mn><mml:mo>,</mml:mo><mml:mi>α</mml:mi><mml:msup><mml:mn>4</mml:mn><mml:mo>'</mml:mo></mml:msup></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq8-2922906.gif"/></alternatives></inline-formula> and <inline-formula><tex-math notation="LaTeX">$\alpha 4$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>α</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:math><inline-graphic xlink:href="ding-ieq9-2922906.gif"/></alternatives></inline-formula> of xyna_theau are identified, consisting mainly of hydrogen bonds, van der Waals forces and π-π stacking. These residue interactions are more resistant to high temperatures than those in xyna_strli. Robust residue interactions within these secondary structures are key factors influencing xyna_strli and xyna_theau thermostability. Analyzing the rigid-community can elucidate the cooperation of secondary structures, which cannot be discovered from sequence and 3D structure alone.